Cellular Traction Force Holds the Potential as a Drug Testing Readout for In Vitro Cancer Metastasis

Introduction Metastasis is responsible for 90% of cancer-related deaths worldwide. However, the potential inhibitory effects of metastasis by various anticancer drugs have been left largely unexplored. Existing preclinical models primarily focus on antiproliferative agents on the primary tumor to ha...

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Veröffentlicht in:Cellular and molecular bioengineering 2024-06, Vol.17 (3), p.203-217
Hauptverfasser: Liew, Hui Yan, Liew, Xiao Hui, Lin, Wei Xuan, Lee, Yee Zhen, Ong, Yong Sze, Ogawa, Satoshi, Chong, Lor Huai
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container_title Cellular and molecular bioengineering
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creator Liew, Hui Yan
Liew, Xiao Hui
Lin, Wei Xuan
Lee, Yee Zhen
Ong, Yong Sze
Ogawa, Satoshi
Chong, Lor Huai
description Introduction Metastasis is responsible for 90% of cancer-related deaths worldwide. However, the potential inhibitory effects of metastasis by various anticancer drugs have been left largely unexplored. Existing preclinical models primarily focus on antiproliferative agents on the primary tumor to halt the cancer growth but not in metastasis. Unlike primary tumors, metastasis requires cancer cells to exert sufficient cellular traction force through the actomyosin machinery to migrate away from the primary tumor site. Therefore, we seek to explore the potential of cellular traction force as a novel readout for screening drugs that target cancer metastasis. Methods In vitro models of invasive and non-invasive breast cancer were first established using MDA-MB-231 and MCF-7 cell lines, respectively. Cellular morphology was characterized, revealing spindle-like morphology in MDA-MB-231 and spherical morphology in MCF-7 cells. The baseline cellular traction force was quantified using the Traction force Microscopy technique. Cisplatin, a paradigm antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, were selected to evaluate the potential of cellular traction force as a drug testing readout for the in vitro cancer metastasis. Results MDA-MB-231 cells exhibited significantly higher baseline cellular traction force compared to MCF-7 cells. Treatment with Cisplatin, an antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, demonstrated distinct effects on cellular traction force in MDA-MB-231 but not in MCF-7 cells. These findings correlate with the invasive potential observed in the two models. Conclusion Cellular traction force emerges as a promising metric for evaluating drug efficacy in inhibiting cancer metastasis using in vitro models. This approach could enhance the screening and development of novel anti-metastatic therapies, addressing a critical gap in current anticancer drug research.
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However, the potential inhibitory effects of metastasis by various anticancer drugs have been left largely unexplored. Existing preclinical models primarily focus on antiproliferative agents on the primary tumor to halt the cancer growth but not in metastasis. Unlike primary tumors, metastasis requires cancer cells to exert sufficient cellular traction force through the actomyosin machinery to migrate away from the primary tumor site. Therefore, we seek to explore the potential of cellular traction force as a novel readout for screening drugs that target cancer metastasis. Methods In vitro models of invasive and non-invasive breast cancer were first established using MDA-MB-231 and MCF-7 cell lines, respectively. Cellular morphology was characterized, revealing spindle-like morphology in MDA-MB-231 and spherical morphology in MCF-7 cells. The baseline cellular traction force was quantified using the Traction force Microscopy technique. Cisplatin, a paradigm antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, were selected to evaluate the potential of cellular traction force as a drug testing readout for the in vitro cancer metastasis. Results MDA-MB-231 cells exhibited significantly higher baseline cellular traction force compared to MCF-7 cells. Treatment with Cisplatin, an antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, demonstrated distinct effects on cellular traction force in MDA-MB-231 but not in MCF-7 cells. These findings correlate with the invasive potential observed in the two models. Conclusion Cellular traction force emerges as a promising metric for evaluating drug efficacy in inhibiting cancer metastasis using in vitro models. This approach could enhance the screening and development of novel anti-metastatic therapies, addressing a critical gap in current anticancer drug research.</description><identifier>ISSN: 1865-5025</identifier><identifier>EISSN: 1865-5033</identifier><identifier>DOI: 10.1007/s12195-024-00811-4</identifier><identifier>PMID: 39050509</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>5-Fluorouracil ; Actomyosin ; Anticancer properties ; Antineoplastic drugs ; Biological and Medical Physics ; Biomaterials ; Biomedical Engineering and Bioengineering ; Biomedical Engineering/Biotechnology ; Biophysics ; Breast cancer ; Cancer ; Cell Biology ; Cell culture ; Cell morphology ; Chemotherapy ; Cisplatin ; Drug efficacy ; Drug screening ; Drug testing ; Drugs ; Engineering ; In vitro methods and tests ; Invasiveness ; Metastases ; Metastasis ; Morphology ; Original ; Original Article ; Traction force ; Tumor cell lines ; Tumors</subject><ispartof>Cellular and molecular bioengineering, 2024-06, Vol.17 (3), p.203-217</ispartof><rights>The Author(s) 2024</rights><rights>The Author(s) 2024.</rights><rights>The Author(s) 2024. 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Mol. Bioeng</addtitle><addtitle>Cell Mol Bioeng</addtitle><description>Introduction Metastasis is responsible for 90% of cancer-related deaths worldwide. However, the potential inhibitory effects of metastasis by various anticancer drugs have been left largely unexplored. Existing preclinical models primarily focus on antiproliferative agents on the primary tumor to halt the cancer growth but not in metastasis. Unlike primary tumors, metastasis requires cancer cells to exert sufficient cellular traction force through the actomyosin machinery to migrate away from the primary tumor site. Therefore, we seek to explore the potential of cellular traction force as a novel readout for screening drugs that target cancer metastasis. Methods In vitro models of invasive and non-invasive breast cancer were first established using MDA-MB-231 and MCF-7 cell lines, respectively. Cellular morphology was characterized, revealing spindle-like morphology in MDA-MB-231 and spherical morphology in MCF-7 cells. The baseline cellular traction force was quantified using the Traction force Microscopy technique. Cisplatin, a paradigm antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, were selected to evaluate the potential of cellular traction force as a drug testing readout for the in vitro cancer metastasis. Results MDA-MB-231 cells exhibited significantly higher baseline cellular traction force compared to MCF-7 cells. Treatment with Cisplatin, an antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, demonstrated distinct effects on cellular traction force in MDA-MB-231 but not in MCF-7 cells. These findings correlate with the invasive potential observed in the two models. Conclusion Cellular traction force emerges as a promising metric for evaluating drug efficacy in inhibiting cancer metastasis using in vitro models. 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Mol. Bioeng</stitle><addtitle>Cell Mol Bioeng</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>17</volume><issue>3</issue><spage>203</spage><epage>217</epage><pages>203-217</pages><issn>1865-5025</issn><eissn>1865-5033</eissn><abstract>Introduction Metastasis is responsible for 90% of cancer-related deaths worldwide. However, the potential inhibitory effects of metastasis by various anticancer drugs have been left largely unexplored. Existing preclinical models primarily focus on antiproliferative agents on the primary tumor to halt the cancer growth but not in metastasis. Unlike primary tumors, metastasis requires cancer cells to exert sufficient cellular traction force through the actomyosin machinery to migrate away from the primary tumor site. Therefore, we seek to explore the potential of cellular traction force as a novel readout for screening drugs that target cancer metastasis. Methods In vitro models of invasive and non-invasive breast cancer were first established using MDA-MB-231 and MCF-7 cell lines, respectively. Cellular morphology was characterized, revealing spindle-like morphology in MDA-MB-231 and spherical morphology in MCF-7 cells. The baseline cellular traction force was quantified using the Traction force Microscopy technique. Cisplatin, a paradigm antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, were selected to evaluate the potential of cellular traction force as a drug testing readout for the in vitro cancer metastasis. Results MDA-MB-231 cells exhibited significantly higher baseline cellular traction force compared to MCF-7 cells. Treatment with Cisplatin, an antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, demonstrated distinct effects on cellular traction force in MDA-MB-231 but not in MCF-7 cells. These findings correlate with the invasive potential observed in the two models. Conclusion Cellular traction force emerges as a promising metric for evaluating drug efficacy in inhibiting cancer metastasis using in vitro models. This approach could enhance the screening and development of novel anti-metastatic therapies, addressing a critical gap in current anticancer drug research.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>39050509</pmid><doi>10.1007/s12195-024-00811-4</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-1491-2524</orcidid><oa>free_for_read</oa></addata></record>
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subjects 5-Fluorouracil
Actomyosin
Anticancer properties
Antineoplastic drugs
Biological and Medical Physics
Biomaterials
Biomedical Engineering and Bioengineering
Biomedical Engineering/Biotechnology
Biophysics
Breast cancer
Cancer
Cell Biology
Cell culture
Cell morphology
Chemotherapy
Cisplatin
Drug efficacy
Drug screening
Drug testing
Drugs
Engineering
In vitro methods and tests
Invasiveness
Metastases
Metastasis
Morphology
Original
Original Article
Traction force
Tumor cell lines
Tumors
title Cellular Traction Force Holds the Potential as a Drug Testing Readout for In Vitro Cancer Metastasis
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