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Higher cell stiffness indicating lower metastatic potential in B16 melanoma cell variants and in (−)-epigallocatechin gallate-treated cells

Purpose To understand how nanomechanical stiffness affects metastatic potential, we studied the relationship between cell migration, a characteristic of metastasis, and cell stiffness using atomic force microscopy (AFM), which can measure stiffness (elasticity) of individual living cells. Methods Mi...

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Published in:Journal of cancer research and clinical oncology 2012-05, Vol.138 (5), p.859-866
Main Authors: Watanabe, Tatsuro, Kuramochi, Hiromi, Takahashi, Atsushi, Imai, Kazue, Katsuta, Naoko, Nakayama, Tomonobu, Fujiki, Hirota, Suganuma, Masami
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cited_by cdi_FETCH-LOGICAL-c516t-b3ea0725cd2473e53820f6755ec1ea7eb996a530ebbd235fc50ee2b16402b7683
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container_title Journal of cancer research and clinical oncology
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creator Watanabe, Tatsuro
Kuramochi, Hiromi
Takahashi, Atsushi
Imai, Kazue
Katsuta, Naoko
Nakayama, Tomonobu
Fujiki, Hirota
Suganuma, Masami
description Purpose To understand how nanomechanical stiffness affects metastatic potential, we studied the relationship between cell migration, a characteristic of metastasis, and cell stiffness using atomic force microscopy (AFM), which can measure stiffness (elasticity) of individual living cells. Methods Migration and cell stiffness of three metastatic B16 melanoma variants (B16-F10, B16-BL6, and B16-F1 cells), and also effects of (−)-epigallocatechin gallate (EGCG), were studied using Transwell assay and AFM. Results Migration of B16-F10 and B16-BL6 cells was 3 and 2 times higher than that of B16-F1 cells in Transwell assay, and cell stiffness determined by AFM was also different among the three variants, although they have similar morphologies and the same growth rates: Means of Young’s modulus were 350.8 ± 4.8 Pa for B16-F10 cells, 661.9 ± 16.5 Pa for B16-BL6 cells, and 727.2 ± 13.0 Pa for B16-F1 cells. AFM measurements revealed that highly motile B16-F10 cells have low cell stiffness, and low motile and metastatic B16-F1 cells have high cell stiffness: Nanomechanical stiffness is inversely correlated with migration potential. Treatment of highly motile B16-F10 cells with EGCG increased cell stiffness 2-fold and inhibited migration of the cells. Conclusions Our study with AFM clearly demonstrates that cell stiffness is a reliable quantitative indicator of migration potential, and very likely metastatic potential, even in morphologically similar cells. And increased cell stiffness may be a key nanomechanical feature in inhibition of metastasis.
doi_str_mv 10.1007/s00432-012-1159-5
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Methods Migration and cell stiffness of three metastatic B16 melanoma variants (B16-F10, B16-BL6, and B16-F1 cells), and also effects of (−)-epigallocatechin gallate (EGCG), were studied using Transwell assay and AFM. Results Migration of B16-F10 and B16-BL6 cells was 3 and 2 times higher than that of B16-F1 cells in Transwell assay, and cell stiffness determined by AFM was also different among the three variants, although they have similar morphologies and the same growth rates: Means of Young’s modulus were 350.8 ± 4.8 Pa for B16-F10 cells, 661.9 ± 16.5 Pa for B16-BL6 cells, and 727.2 ± 13.0 Pa for B16-F1 cells. AFM measurements revealed that highly motile B16-F10 cells have low cell stiffness, and low motile and metastatic B16-F1 cells have high cell stiffness: Nanomechanical stiffness is inversely correlated with migration potential. Treatment of highly motile B16-F10 cells with EGCG increased cell stiffness 2-fold and inhibited migration of the cells. Conclusions Our study with AFM clearly demonstrates that cell stiffness is a reliable quantitative indicator of migration potential, and very likely metastatic potential, even in morphologically similar cells. And increased cell stiffness may be a key nanomechanical feature in inhibition of metastasis.</description><identifier>ISSN: 0171-5216</identifier><identifier>EISSN: 1432-1335</identifier><identifier>DOI: 10.1007/s00432-012-1159-5</identifier><identifier>PMID: 22297840</identifier><identifier>CODEN: JCROD7</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Animals ; Anticarcinogenic Agents - pharmacology ; Antineoplastic agents ; Biological and medical sciences ; Cancer Research ; Catechin - analogs &amp; derivatives ; Catechin - pharmacology ; Cell Movement - drug effects ; Cellular biology ; Elastic Modulus - drug effects ; Elasticity - drug effects ; Hematology ; Internal Medicine ; Medical sciences ; Medicine ; Medicine &amp; Public Health ; Melanoma, Experimental - drug therapy ; Melanoma, Experimental - secondary ; Metastasis ; Mice ; Microscopy ; Microscopy, Atomic Force ; Oncology ; Original Paper ; Pharmacology. 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Methods Migration and cell stiffness of three metastatic B16 melanoma variants (B16-F10, B16-BL6, and B16-F1 cells), and also effects of (−)-epigallocatechin gallate (EGCG), were studied using Transwell assay and AFM. Results Migration of B16-F10 and B16-BL6 cells was 3 and 2 times higher than that of B16-F1 cells in Transwell assay, and cell stiffness determined by AFM was also different among the three variants, although they have similar morphologies and the same growth rates: Means of Young’s modulus were 350.8 ± 4.8 Pa for B16-F10 cells, 661.9 ± 16.5 Pa for B16-BL6 cells, and 727.2 ± 13.0 Pa for B16-F1 cells. AFM measurements revealed that highly motile B16-F10 cells have low cell stiffness, and low motile and metastatic B16-F1 cells have high cell stiffness: Nanomechanical stiffness is inversely correlated with migration potential. Treatment of highly motile B16-F10 cells with EGCG increased cell stiffness 2-fold and inhibited migration of the cells. Conclusions Our study with AFM clearly demonstrates that cell stiffness is a reliable quantitative indicator of migration potential, and very likely metastatic potential, even in morphologically similar cells. And increased cell stiffness may be a key nanomechanical feature in inhibition of metastasis.</description><subject>Animals</subject><subject>Anticarcinogenic Agents - pharmacology</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Cancer Research</subject><subject>Catechin - analogs &amp; derivatives</subject><subject>Catechin - pharmacology</subject><subject>Cell Movement - drug effects</subject><subject>Cellular biology</subject><subject>Elastic Modulus - drug effects</subject><subject>Elasticity - drug effects</subject><subject>Hematology</subject><subject>Internal Medicine</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Melanoma, Experimental - drug therapy</subject><subject>Melanoma, Experimental - secondary</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Microscopy</subject><subject>Microscopy, Atomic Force</subject><subject>Oncology</subject><subject>Original Paper</subject><subject>Pharmacology. 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Methods Migration and cell stiffness of three metastatic B16 melanoma variants (B16-F10, B16-BL6, and B16-F1 cells), and also effects of (−)-epigallocatechin gallate (EGCG), were studied using Transwell assay and AFM. Results Migration of B16-F10 and B16-BL6 cells was 3 and 2 times higher than that of B16-F1 cells in Transwell assay, and cell stiffness determined by AFM was also different among the three variants, although they have similar morphologies and the same growth rates: Means of Young’s modulus were 350.8 ± 4.8 Pa for B16-F10 cells, 661.9 ± 16.5 Pa for B16-BL6 cells, and 727.2 ± 13.0 Pa for B16-F1 cells. AFM measurements revealed that highly motile B16-F10 cells have low cell stiffness, and low motile and metastatic B16-F1 cells have high cell stiffness: Nanomechanical stiffness is inversely correlated with migration potential. Treatment of highly motile B16-F10 cells with EGCG increased cell stiffness 2-fold and inhibited migration of the cells. Conclusions Our study with AFM clearly demonstrates that cell stiffness is a reliable quantitative indicator of migration potential, and very likely metastatic potential, even in morphologically similar cells. And increased cell stiffness may be a key nanomechanical feature in inhibition of metastasis.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>22297840</pmid><doi>10.1007/s00432-012-1159-5</doi><tpages>8</tpages></addata></record>
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subjects Animals
Anticarcinogenic Agents - pharmacology
Antineoplastic agents
Biological and medical sciences
Cancer Research
Catechin - analogs & derivatives
Catechin - pharmacology
Cell Movement - drug effects
Cellular biology
Elastic Modulus - drug effects
Elasticity - drug effects
Hematology
Internal Medicine
Medical sciences
Medicine
Medicine & Public Health
Melanoma, Experimental - drug therapy
Melanoma, Experimental - secondary
Metastasis
Mice
Microscopy
Microscopy, Atomic Force
Oncology
Original Paper
Pharmacology. Drug treatments
Skin Neoplasms - drug therapy
Skin Neoplasms - pathology
title Higher cell stiffness indicating lower metastatic potential in B16 melanoma cell variants and in (−)-epigallocatechin gallate-treated cells
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