Startseite Chemotherapeutic resistance: a nano-mechanical point of view
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Chemotherapeutic resistance: a nano-mechanical point of view

  • Collins Otieno Nyongesa

    Collins Nyongesa is working in the group of Dr. Soyeun Park as a graduate student at the College of Pharmacy at Keimyung University. He is investigating the effect of the interplay between cancer cells and the artificially controlled environments on anti-cancer drug resistance.

    und Soyeun Park

    Soyeun Park is an Associate Professor at the College of Pharmacy at Keimyung University. She has been investigating the role of mechanical properties of cancer cells in cancer onset, progression, and anti-cancer drug efficacy using biophysical and biochemical tools including atomic force microscopy and nano-patterned substrates.

    EMAIL logo
Veröffentlicht/Copyright: 23. August 2018

Abstract

Chemotherapeutic resistance is one of the main obstacles for cancer remission. To understand how cancer cells acquire chemotherapeutic resistance, biochemical studies focusing on drug target alteration, altered cell proliferation, and reduced susceptibility to apoptosis were performed. Advances in nano-mechanobiology showed that the enhanced mechanical deformability of cancer cells accompanied by cytoskeletal alteration is a decisive factor for cancer development. Furthermore, atomic force microscopy (AFM)–based nano-mechanical studies showed that chemotherapeutic treatments reinforced the mechanical stiffness of drug-sensitive cancer cells. However, drug-resistant cancer cells did not show such mechanical responses following chemotherapeutic treatments. Interestingly, drug-resistant cancer cells are mechanically heterogeneous, with a subpopulation of resistant cells showing higher stiffness than their drug-sensitive counterparts. The signaling pathways involving Rho, vinculin, and myosin II were found to be responsible for these mechanical alterations in drug-resistant cancer cells. In the present review, we highlight the mechanical aspects of chemotherapeutic resistance, and suggest how mechanical studies can contribute to unravelling the multifaceted nature of chemotherapeutic resistance.

Award Identifier / Grant number: 2015R1C1A2A01052717

Funding source: Ministry of Education

Award Identifier / Grant number: NRF-2018R1D1A3B07050399

Funding statement: This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP; no. 2015R1C1A2A01052717) and the Ministry of Education (no. NRF-2018R1D1A3B07050399).

About the authors

Collins Otieno Nyongesa

Collins Nyongesa is working in the group of Dr. Soyeun Park as a graduate student at the College of Pharmacy at Keimyung University. He is investigating the effect of the interplay between cancer cells and the artificially controlled environments on anti-cancer drug resistance.

Soyeun Park

Soyeun Park is an Associate Professor at the College of Pharmacy at Keimyung University. She has been investigating the role of mechanical properties of cancer cells in cancer onset, progression, and anti-cancer drug efficacy using biophysical and biochemical tools including atomic force microscopy and nano-patterned substrates.

References

Aspenstrom, P. (2014). Atypical Rho GTPases RhoD and Rif integrate cytoskeletal dynamics and membrane trafficking. Biol. Chem. 395, 477–484.10.1515/hsz-2013-0296Suche in Google Scholar PubMed

Au, N.P., Fang, Y., Xi, N., Lai, K.W., and Ma, C.H. (2014). Probing for chemotherapy-induced peripheral neuropathy in live dorsal root ganglion neurons with atomic force microscopy. Nanomedicine 10, 1323–1333.10.1016/j.nano.2014.03.002Suche in Google Scholar PubMed

Baines, A.T., Xu, D., and Der, C.J. (2011). Inhibition of Ras for cancer treatment: the search continues. Future Med. Chem. 3, 1787–1808.10.4155/fmc.11.121Suche in Google Scholar PubMed PubMed Central

Bashir, Y., Geelani, S., Bashir, N., Mir, S.A., Mushtaq, M., Jan, M.A., and Rasool, J. (2015). Role of low dose cytarabine in elderly patients with acute myeloid leukemia: an experience. South Asian J. Cancer 4, 4–6.10.4103/2278-330X.149918Suche in Google Scholar PubMed PubMed Central

Bastatas, L., Martinez-Marin, D., Matthews, J., Hashem, J., Lee, Y.J., Sennoune, S., Filleur, S., Martinez-Zaguilan, R., and Park, S. (2012). AFM nano-mechanics and calcium dynamics of prostate cancer cells with distinct metastatic potential. Biochim. Biophys. Acta 1820, 1111–1120.10.1016/j.bbagen.2012.02.006Suche in Google Scholar PubMed

Beil, M., Micoulet, A., Von Wichert, G., Paschke, S., Walther, P., Omary, M.B., Van Veldhoven, P.P., Gern, U., Wolff-Hieber, E., Eggermann, J., et al. (2003). Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells. Nat. Cell Biol. 5, 803–811.10.1038/ncb1037Suche in Google Scholar PubMed

Braet, F., Spector, I., De Zanger, R., and Wisse, E. (1998). A novel structure involved in the formation of liver endothelial cell fenestrae revealed by using the actin inhibitor misakinolide. Proc. Natl. Acad. Sci. USA 95, 13635–13640.10.1073/pnas.95.23.13635Suche in Google Scholar PubMed PubMed Central

Chen, C., Yin, L., Song, X., Yang, H., Ren, X., Gong, X., Wang, F., and Yang, L. (2016). Effects of vimentin disruption on the mechanoresponses of articular chondrocyte. Biochem. Biophys. Res. Commun. 469, 132–137.10.1016/j.bbrc.2015.11.083Suche in Google Scholar PubMed

Coleman, R.L. (2002). Emerging role of topotecan in front-line treatment of carcinoma of the ovary. Oncologist 7(Suppl 5), 46–55.10.1634/theoncologist.7-suppl_5-46Suche in Google Scholar PubMed

Cross, S.E., Jin, Y.S., Rao, J., and Gimzewski, J.K. (2007). Nanomechanical analysis of cells from cancer patients. Nat. Nanotechnol. 2, 780–783.10.1201/9780429399039-18Suche in Google Scholar

Cross, S.E., Jin, Y.S., Lu, Q.Y., Rao, J., and Gimzewski, J.K. (2011). Green tea extract selectively targets nanomechanics of live metastatic cancer cells. Nanotechnology 22, 215101.10.1088/0957-4484/22/21/215101Suche in Google Scholar PubMed PubMed Central

Cui, Y., Zhang, X., You, K., Guo, Y., Liu, C., Fang, X., and Geng, L. (2017). Nanomechanical characteristics of cervical cancer and cervical intraepithelial neoplasia revealed by atomic force microscopy. Med. Sci. Monit. 23, 4205–4213.10.12659/MSM.903484Suche in Google Scholar

Cunningham, C.C., Gorlin, J.B., Kwiatkowski, D.J., Hartwig, J.H., Janmey, P.A., Byers, H.R., and Stossel, T.P. (1992). Actin-binding protein requirement for cortical stability and efficient locomotion. Science 255, 325–327.10.1126/science.1549777Suche in Google Scholar PubMed

Dagogo-Jack, I. and Shaw, A.T. (2018). Tumour heterogeneity and resistance to cancer therapies. Nat. Rev. Clin. Oncol. 15, 81–94.10.1038/nrclinonc.2017.166Suche in Google Scholar PubMed

Darling, E.M., Zauscher, S., Block, J.A., and Guilak, F. (2007). A thin-layer model for viscoelastic, stress-relaxation testing of cells using atomic force microscopy: do cell properties reflect metastatic potential? Biophys. J. 92, 1784–1791.10.1529/biophysj.106.083097Suche in Google Scholar PubMed PubMed Central

Dickreuter, E. and Cordes, N. (2017). The cancer cell adhesion resistome: mechanisms, targeting and translational approaches. Biol. Chem. 398, 721–735.10.1515/hsz-2016-0326Suche in Google Scholar PubMed

Dumontet, C. and Jordan, M.A. (2010). Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat. Rev. Drug Discov. 9, 790–803.10.1038/nrd3253Suche in Google Scholar PubMed PubMed Central

Efremov, Y.M., Wang, W.H., Hardy, S.D., Geahlen, R.L., and Raman, A. (2017). Measuring nanoscale viscoelastic parameters of cells directly from AFM force-displacement curves. Sci. Rep. 7, 1541.10.1038/s41598-017-01784-3Suche in Google Scholar PubMed PubMed Central

Faria, E.C., Ma, N., Gazi, E., Gardner, P., Brown, M., Clarke, N.W., and Snook, R.D. (2008). Measurement of elastic properties of prostate cancer cells using AFM. Analyst 133, 1498–1500.10.1039/b803355bSuche in Google Scholar PubMed

Fisher, R., Pusztai, L., and Swanton, C. (2013). Cancer heterogeneity: implications for targeted therapeutics. Br. J. Cancer 108, 479–485.10.1038/bjc.2012.581Suche in Google Scholar PubMed PubMed Central

Fleisher, M. (1993). Antifolate analogs: mechanism of action, analytical methodology, and clinical efficacy. Ther. Drug Monit. 15, 521–526.10.1097/00007691-199312000-00012Suche in Google Scholar

Fletcher, D.A. and Mullins, R.D. (2010). Cell mechanics and the cytoskeleton. Nature 463, 485–492.10.1038/nature08908Suche in Google Scholar PubMed PubMed Central

Fraczkowska, K., Bacia, M., Przybylo, M., Drabik, D., Kaczorowska, A., Rybka, J., Stefanko, E., Drobczynski, S., Masajada, J., Podbielska, H., et al. (2018). Alterations of biomechanics in cancer and normal cells induced by doxorubicin. Biomed. Pharmacother. 97, 1195–1203.10.1016/j.biopha.2017.11.040Suche in Google Scholar PubMed

Fu, J., Wang, Y.K., Yang, M.T., Desai, R.A., Yu, X., Liu, Z., and Chen, C.S. (2010). Mechanical regulation of cell function with geometrically modulated elastomeric substrates. Nat. Methods 7, 733–736.10.1038/nmeth.1487Suche in Google Scholar PubMed PubMed Central

Fuhr, G., Richter, E., Zimmermann, H., Hitzler, H., Niehus, H., and Hagedorn, R. (1998). Cell traces–footprints of individual cells during locomotion and adhesion. Biol. Chem. 379, 1161–1173.10.1515/bchm.1998.379.8-9.1161Suche in Google Scholar PubMed

Fukuyama, K., Tzeng, S., Sakamoto, M., and Epstein, W.L. (1980). Effects of trace elements in polymerization of keratin proteins and destruction of the filaments by processing techniques for electron microscopy. Curr. Probl. Dermatol. 10, 407–420.10.1159/000396304Suche in Google Scholar PubMed

Gardel, M.L., Shin, J.H., Mackintosh, F.C., Mahadevan, L., Matsudaira, P., and Weitz, D.A. (2004). Elastic behavior of cross-linked and bundled actin networks. Science 304, 1301–1305.10.1126/science.1095087Suche in Google Scholar PubMed

Gibbs, J.B. (2000). Anticancer drug targets: growth factors and growth factor signaling. J. Clin. Invest. 105, 9–13.10.1172/JCI9084Suche in Google Scholar PubMed PubMed Central

Gladilin, E., Gonzalez, P., and Eils, R. (2014). Dissecting the contribution of actin and vimentin intermediate filaments to mechanical phenotype of suspended cells using high- throughput deformability measurements and computational modeling. J. Biomech. 47, 2598–2605.10.1016/j.jbiomech.2014.05.020Suche in Google Scholar PubMed

Gossett, D.R., Tse, H.T., Lee, S.A., Ying, Y., Lindgren, A.G., Yang, O.O., Rao, J., Clark, A.T., and Di Carlo, D. (2012). Hydrodynamic stretching of single cells for large population mechanical phenotyping. Proc. Natl. Acad. Sci. USA 109, 7630–7635.10.1073/pnas.1200107109Suche in Google Scholar PubMed PubMed Central

Greenstein, S., Ghias, K., Krett, N.L., and Rosen, S.T. (2002). Mechanisms of glucocorticoid-mediated apoptosis in hematological malignancies. Clin. Cancer Res. 8, 1681–1694.Suche in Google Scholar

Grzanka, A., Grzanka, D., and Orlikowska, M. (2003). Cytoskeletal reorganization during process of apoptosis induced by cytostatic drugs in K-562 and HL-60 leukemia cell lines. Biochem. Pharmacol. 66, 1611–1617.10.1016/S0006-2952(03)00532-XSuche in Google Scholar

Guck, J., Schinkinger, S., Lincoln, B., Wottawah, F., Ebert, S., Romeyke, M., Lenz, D., Erickson, H.M., Ananthakrishnan, R., Mitchell, D., et al. (2005). Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys. J. 88, 3689–3698.10.1529/biophysj.104.045476Suche in Google Scholar

Guevorkian, K. and Maitre, J.L. (2017). Micropipette aspiration: a unique tool for exploring cell and tissue mechanics in vivo. Methods Cell Biol. 139, 187–201.10.1016/bs.mcb.2016.11.012Suche in Google Scholar

Hagner, N. and Joerger, M. (2010). Cancer chemotherapy: targeting folic acid synthesis. Cancer Manag. Res. 2, 293–301.10.2147/CMAR.S10043Suche in Google Scholar

Hall, A.G. and Tilby, M.J. (1992). Mechanisms of action of, and modes of resistance to, alkylating agents used in the treatment of haematological malignancies. Blood Rev. 6, 163–173.10.1016/0268-960X(92)90028-OSuche in Google Scholar

Hu, S., Liu, G., Chen, W., Li, X., Lu, W., Lam, R.H., and Fu, J. (2016). Multiparametric biomechanical and biochemical phenotypic profiling of single cancer cells using an elasticity microcytometer. Small 12, 2300–2311.10.1002/smll.201503620Suche in Google Scholar PubMed PubMed Central

Jaffe, A.B. and Hall, A. (2005). Rho GTPases: biochemistry and biology. Annu. Rev. Cell Dev. Biol. 21, 247–269.10.1146/annurev.cellbio.21.020604.150721Suche in Google Scholar PubMed

Kapoor, A., Barai, A., Thakur, B., Das, A., Patwardhan, S.R., Monteiro, M., Gaikwad, S., Bukhari, A.B., Mogha, P., Majumder, A., et al. (2018). Soft drug-resistant ovarian cancer cells migrate via two distinct mechanisms utilizing myosin II-based contractility. Biochim. Biophys. Acta 1865, 392–405.10.1016/j.bbamcr.2017.11.012Suche in Google Scholar PubMed

Lam, W.A., Rosenbluth, M.J., and Fletcher, D.A. (2007). Chemotherapy exposure increases leukemia cell stiffness. Blood 109, 3505–3508.10.1182/blood-2006-08-043570Suche in Google Scholar PubMed PubMed Central

Larionov, A.A. (2018). Current therapies for human epidermal growth factor receptor 2-positive metastatic breast cancer patients. Front. Oncol. 8, 89.10.3389/fonc.2018.00089Suche in Google Scholar PubMed PubMed Central

Lavinsky, R.M., Jepsen, K., Heinzel, T., Torchia, J., Mullen, T.M., Schiff, R., Del-Rio, A.L., Ricote, M., Ngo, S., Gemsch, J., et al. (1998). Diverse signaling pathways modulate nuclear receptor recruitment of N-CoR and SMRT complexes. Proc. Natl. Acad. Sci. USA 95, 2920–2925.10.1073/pnas.95.6.2920Suche in Google Scholar PubMed PubMed Central

Lekka, M. and Laidler, P. (2009). Applicability of AFM in cancer detection. Nat. Nanotechnol 4, 72; author reply 72–73.10.1038/nnano.2009.004Suche in Google Scholar

Lekka, M., Laidler, P., Gil, D., Lekki, J., Stachura, Z., and Hrynkiewicz, A.Z. (1999). Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy. Eur. Biophys. J. 28, 312–316.10.1007/s002490050213Suche in Google Scholar

Lekka, M., Laidler, P., Ignacak, J., Labedz, M., Lekki, J., Struszczyk, H., Stachura, Z., and Hrynkiewicz, A.Z. (2001). The effect of chitosan on stiffness and glycolytic activity of human bladder cells. Biochim. Biophys. Acta 1540, 127–136.10.1016/S0167-4889(01)00125-2Suche in Google Scholar

Li, Q.S., Lee, G.Y., Ong, C.N., and Lim, C.T. (2008). AFM indentation study of breast cancer cells. Biochem. Biophys. Res. Commun. 374, 609–613.10.1016/j.bbrc.2008.07.078Suche in Google Scholar PubMed

Li, M., Liu, L., Xi, N., Wang, Y., Dong, Z., Xiao, X., and Zhang, W. (2012). Drug-induced changes of topography and elasticity in living B lymphoma cells based on atomic force microscopy. Acta Phys. Chim. Sin. 28, 1502–1508.10.3866/PKU.WHXB201203201Suche in Google Scholar

Li, M., Liu, L., Xi, N., Wang, Y., Xiao, X., and Zhang, W. (2015). Quantitative analysis of drug-induced complement-mediated cytotoxic effect on single tumor cells using atomic force microscopy and fluorescence microscopy. IEEE Trans. Nanobiosci. 14, 84–94.10.1109/TNB.2014.2370759Suche in Google Scholar PubMed

Li, M., Liu, L., Xiao, X., Xi, N., and Wang, Y. (2016a). Effects of methotrexate on the viscoelastic properties of single cells probed by atomic force microscopy. J. Biol. Phys. 42, 551–569.10.1007/s10867-016-9423-6Suche in Google Scholar PubMed PubMed Central

Li, M., Xiao, X., Liu, L., Xi, N., and Wang, Y. (2016b). Nanoscale quantifying the effects of targeted drug on chemotherapy in lymphoma treatment using atomic force microscopy. IEEE Trans. Biomed. Eng. 63, 2187–2199.10.1109/TBME.2015.2512924Suche in Google Scholar PubMed

Li, M., Dang, D., Liu, L., Xi, N., and Wang, Y. (2017). Atomic force microscopy in characterizing cell mechanics for biomedical applications: a review. IEEE Trans. Nanobiosci. 16, 523–540.10.1109/TNB.2017.2714462Suche in Google Scholar PubMed

Lin, K.T. and Wang, L.H. (2016). New dimension of glucocorticoids in cancer treatment. Steroids 111, 84–88.10.1016/j.steroids.2016.02.019Suche in Google Scholar PubMed

Lin, H.H., Lin, H.K., Lin, I.H., Chiou, Y.W., Chen, H.W., Liu, C.Y., Harn, H.I., Chiu, W.T., Wang, Y.K., Shen, M.R., et al. (2015). Mechanical phenotype of cancer cells: cell softening and loss of stiffness sensing. Oncotarget 6, 20946–20958.10.18632/oncotarget.4173Suche in Google Scholar

Modjtahedi, H., Ali, S., and Essapen, S. (2012). Therapeutic application of monoclonal antibodies in cancer: advances and challenges. Br. Med. Bull. 104, 41–59.10.1093/bmb/lds032Suche in Google Scholar

Moeendarbary, E. and Harris, A.R. (2014). Cell mechanics: principles, practices, and prospects. Wiley Interdiscip. Rev. Syst. Biol. Med. 6, 371–388.10.1002/wsbm.1275Suche in Google Scholar

Mogilner, A. and Oster, G. (1996). Cell motility driven by actin polymerization. Biophys. J. 71, 3030–3045.10.1016/S0006-3495(96)79496-1Suche in Google Scholar

Montecucco, A., Zanetta, F., and Biamonti, G. (2015). Molecular mechanisms of etoposide. Excli. J. 14, 95–108.Suche in Google Scholar

Moustakas, A. and Stournaras, C. (1999). Regulation of actin organisation by TGF-β in H-ras-transformed fibroblasts. J. Cell Sci. 112, 1169–1179.10.1242/jcs.112.8.1169Suche in Google Scholar

Mukohara, T. (2011). Mechanisms of resistance to anti-human epidermal growth factor receptor 2 agents in breast cancer. Cancer Sci. 102, 1–8.10.1111/j.1349-7006.2010.01711.xSuche in Google Scholar

Munevar, S., Wang, Y., and Dembo, M. (2001). Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts. Biophys. J. 80, 1744–1757.10.1016/S0006-3495(01)76145-0Suche in Google Scholar

Nalbant, P. and Dehmelt, L. (2018). Exploratory cell dynamics: a sense of touch for cells? Biol. Chem. 399, 809–819.10.1515/hsz-2017-0341Suche in Google Scholar PubMed

Ochalek, T., Nordt, F.J., Tullberg, K., and Burger, M.M. (1988). Correlation between cell deformability and metastatic potential in B16-F1 melanoma cell variants. Cancer Res. 48, 5124–5128.Suche in Google Scholar

Odaka, C., Sanders, M.L., and Crews, P. (2000). Jasplakinolide induces apoptosis in various transformed cell lines by a caspase-3-like protease-dependent pathway. Clin. Diagn. Lab. Immunol. 7, 947–952.10.1128/CDLI.7.6.947-952.2000Suche in Google Scholar PubMed PubMed Central

Park, S. (2016). Nano-mechanical phenotype as a promising biomarker to evaluate cancer development, progression, and anti-cancer drug efficacy. J. Cancer Prev. 21, 73–80.10.15430/JCP.2016.21.2.73Suche in Google Scholar PubMed PubMed Central

Park, S. and Lee, Y.J. (2014). AFM-based dual nano-mechanical phenotypes for cancer metastasis. J. Biol. Phys. 40, 413–419.10.1007/s10867-014-9353-0Suche in Google Scholar PubMed PubMed Central

Parker, W.B. (2009). Enzymology of purine and pyrimidine antimetabolites used in the treatment of cancer. Chem. Rev. 109, 2880–2893.10.1021/cr900028pSuche in Google Scholar PubMed PubMed Central

Paszek, M.J., Zahir, N., Johnson, K.R., Lakins, J.N., Rozenberg, G.I., Gefen, A., Reinhart-King, C.A., Margulies, S.S., Dembo, M., Boettiger, D., et al. (2005). Tensional homeostasis and the malignant phenotype. Cancer Cell 8, 241–254.10.1016/j.ccr.2005.08.010Suche in Google Scholar PubMed

Provenzano, P.P. and Keely, P.J. (2011). Mechanical signaling through the cytoskeleton regulates cell proliferation by coordinated focal adhesion and Rho GTPase signaling. J. Cell Sci. 124, 1195–1205.10.1242/jcs.067009Suche in Google Scholar PubMed PubMed Central

Ramachandran, S., Quist, A.P., Kumar, S., and Lal, R. (2006). Cisplatin nanoliposomes for cancer therapy: AFM and fluorescence imaging of cisplatin encapsulation, stability, cellular uptake, and toxicity. Langmuir 22, 8156–8162.10.1021/la0607499Suche in Google Scholar PubMed

Rebelo, L.M., De Sousa, J.S., Mendes Filho, J., and Radmacher, M. (2013). Comparison of the viscoelastic properties of cells from different kidney cancer phenotypes measured with atomic force microscopy. Nanotechnology 24, 055102.10.1088/0957-4484/24/5/055102Suche in Google Scholar PubMed

Remmerbach, T.W., Wottawah, F., Dietrich, J., Lincoln, B., Wittekind, C., and Guck, J. (2009). Oral cancer diagnosis by mechanical phenotyping. Cancer Res. 69, 1728–1732.10.1158/0008-5472.CAN-08-4073Suche in Google Scholar PubMed

Ren, J., Huang, H., Liu, Y., Zheng, X., and Zou, Q. (2015). An atomic force microscope study revealed two mechanisms in the effect of anticancer drugs on rate-dependent Young’s modulus of human prostate cancer cells. PLoS One 10, e0126107.10.1371/journal.pone.0126107Suche in Google Scholar PubMed PubMed Central

Rosenbluth, M.J., Lam, W.A., and Fletcher, D.A. (2006). Force microscopy of nonadherent cells: a comparison of leukemia cell deformability. Biophys. J. 90, 2994–3003.10.1529/biophysj.105.067496Suche in Google Scholar PubMed PubMed Central

Rother, J., Noding, H., Mey, I., and Janshoff, A. (2014). Atomic force microscopy-based microrheology reveals significant differences in the viscoelastic response between malign and benign cell lines. Open Biol 4, 140046.10.1098/rsob.140046Suche in Google Scholar PubMed PubMed Central

Rotsch, C. and Radmacher, M. (2000). Drug-induced changes of cytoskeletal structure and mechanics in fibroblasts: an atomic force microscopy study. Biophys. J. 78, 520–535.10.1016/S0006-3495(00)76614-8Suche in Google Scholar

Rybinski, B. and Yun, K. (2016). Addressing intra-tumoral heterogeneity and therapy resistance. Oncotarget 7, 72322–72342.10.18632/oncotarget.11875Suche in Google Scholar PubMed PubMed Central

Schoumacher, M., Goldman, R.D., Louvard, D., and Vignjevic, D.M. (2010). Actin, microtubules, and vimentin intermediate filaments cooperate for elongation of invadopodia. J. Cell Biol. 189, 541–556.10.1083/jcb.200909113Suche in Google Scholar PubMed PubMed Central

Seo, Y.H., Jo, Y.N., Oh, Y.J., and Park, S. (2015). Nano-mechanical reinforcement in drug-resistant ovarian cancer cells. Biol. Pharm. Bull. 38, 389–395.10.1248/bpb.b14-00604Suche in Google Scholar PubMed

Sharma, S., Santiskulvong, C., Bentolila, L.A., Rao, J., Dorigo, O., and Gimzewski, J.K. (2012). Correlative nanomechanical profiling with super-resolution F-actin imaging reveals novel insights into mechanisms of cisplatin resistance in ovarian cancer cells. Nanomedicine 8, 757–766.10.1016/j.nano.2011.09.015Suche in Google Scholar PubMed

Sharma, S., Santiskulvong, C., Rao, J., Gimzewski, J.K., and Dorigo, O. (2014). The role of Rho GTPase in cell stiffness and cisplatin resistance in ovarian cancer cells. Integr. Biol. (Cambr.) 6, 611–617.10.1039/C3IB40246KSuche in Google Scholar PubMed

Sheikh, S., Gratzer, W.B., Pinder, J.C., and Nash, G.B. (1997). Actin polymerisation regulates integrin-mediated adhesion as well as rigidity of neutrophils. Biochem. Biophys. Res. Commun. 238, 910–915.10.1006/bbrc.1997.7407Suche in Google Scholar PubMed

Smith, M.R. (2003). Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene 22, 7359–7368.10.1038/sj.onc.1206939Suche in Google Scholar PubMed

Souliotis, V.L., Dimopoulos, M.A., and Sfikakis, P.P. (2003). Gene-specific formation and repair of DNA monoadducts and interstrand cross-links after therapeutic exposure to nitrogen mustards. Clin. Cancer Res. 9, 4465–4474.Suche in Google Scholar

Sun, Y.L., Patel, A., Kumar, P., and Chen, Z.S. (2012). Role of ABC transporters in cancer chemotherapy. Chin. J. Cancer 31, 51–57.10.5732/cjc.011.10466Suche in Google Scholar PubMed PubMed Central

Szakacs, G., Paterson, J.K., Ludwig, J.A., Booth-Genthe, C., and Gottesman, M.M. (2006). Targeting multidrug resistance in cancer. Nat. Rev. Drug Discov. 5, 219–234.10.1038/nrd1984Suche in Google Scholar PubMed

Szulawska, A. and Czyz, M. (2006). [Molecular mechanisms of anthracyclines action]. Postepy Hig Med Dosw (Online) 60, 78–100.Suche in Google Scholar

Tekade, R.K., Tekade, M., Kesharwani, P., and D’emanuele, A. (2016). RNAi-combined nano-chemotherapeutics to tackle resistant tumors. Drug Discov. Today 21, 1761–1774.10.1016/j.drudis.2016.06.029Suche in Google Scholar

Van Vuuren, R.J., Visagie, M.H., Theron, A.E., and Joubert, A.M. (2015). Antimitotic drugs in the treatment of cancer. Cancer Chemother. Pharmacol. 76, 1101–1112.10.1007/s00280-015-2903-8Suche in Google Scholar

Warwick, G.P. (1963). The mechanism of action of alkylating agents. Cancer Res. 23, 1315–1333.Suche in Google Scholar

Watanabe, T., Kuramochi, H., Takahashi, A., Imai, K., Katsuta, N., Nakayama, T., Fujiki, H., and Suganuma, M. (2012). Higher cell stiffness indicating lower metastatic potential in B16 melanoma cell variants and in (-)-epigallocatechin gallate-treated cells. J. Cancer Res. Clin. Oncol. 138, 859–866.10.1007/s00432-012-1159-5Suche in Google Scholar

Webster, N.J., Green, S., Jin, J.R., and Chambon, P. (1988). The hormone-binding domains of the estrogen and glucocorticoid receptors contain an inducible transcription activation function. Cell 54, 199–207.10.1016/0092-8674(88)90552-1Suche in Google Scholar

Wong, R.S. (2011). Apoptosis in cancer: from pathogenesis to treatment. J. Exp. Clin. Cancer Res. 30, 87.10.1186/1756-9966-30-87Suche in Google Scholar PubMed PubMed Central

Wu, H.W., Kuhn, T., and Moy, V.T. (1998). Mechanical properties of L929 cells measured by atomic force microscopy: effects of anticytoskeletal drugs and membrane crosslinking. Scanning 20, 389–397.10.1002/sca.1998.4950200504Suche in Google Scholar PubMed

Xu, W., Mezencev, R., Kim, B., Wang, L., Mcdonald, J., and Sulchek, T. (2012). Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells. PLoS One 7, e46609.10.1371/journal.pone.0046609Suche in Google Scholar PubMed PubMed Central

Yamaguchi, H. and Condeelis, J. (2007). Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim. Biophys. Acta 1773, 642–652.10.1016/j.bbamcr.2006.07.001Suche in Google Scholar PubMed PubMed Central

Zahreddine, H. and Borden, K.L. (2013). Mechanisms and insights into drug resistance in cancer. Front. Pharmacol. 4, 28.10.3389/fphar.2013.00028Suche in Google Scholar PubMed PubMed Central

Zhou, Z., Zheng, C., Li, S., Zhou, X., Liu, Z., He, Q., Zhang, N., Ngan, A., Tang, B., and Wang, A. (2013). AFM nanoindentation detection of the elastic modulus of tongue squamous carcinoma cells with different metastatic potentials. Nanomedicine 9, 864–874.10.1016/j.nano.2013.04.001Suche in Google Scholar PubMed

Received: 2018-06-06
Accepted: 2018-07-19
Published Online: 2018-08-23
Published in Print: 2018-11-27

©2018 Walter de Gruyter GmbH, Berlin/Boston

Heruntergeladen am 6.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/hsz-2018-0274/html
Button zum nach oben scrollen