Investigation of Cellular Traction Force as a Drug Testing Readout for In Vitro Cancer Metastasis

Introduction: Metastasis is responsible for 90% of cancer-related deaths in solid tumors. However, the effects of metastasis in different 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, the process of metastasis requires cancer cells to exert sufficient traction forces through the actomyosin machinery to migrate away from the primary tumor site. Therefore, we aim to explore the potential of traction force as a novel readout for screening drugs that target cancer metastasis.

Materials and Methods: We first established in vitro invasive and non-invasive cancer models using theMDA-MB-231 and MCF-7 cell lines, respectively. We then selected cisplatin and5-fluorouracil (5FU), a paradigm antimetastatic drug and a non-antimetastatic drug respectively, to evaluate the potential of cellular traction force as a readout forin vitro cancer metastasis. Subsequently, we characterize and correlate the cell morphology, invasion assay, and their corresponding traction forces of MCF-7 andMDA-MB-231 following drug treatments.

Results: We observed that the invasive cancer model, MDA-MB-231, displayed an elongated spindle-like morphology, contrasting with the more spherical shape of the non-invasive cell model, MCF-7.We also found that the MDA-MB-231 exhibit a higher average magnitude of force compared to MCF-7. When subjected to drug treatment, our results demonstrated a significant difference in the average magnitude of cellular traction force betweenMDA-MB-231 and MCF-7 in response to the drugs.

Discussion: Through the correlation of cell morphology, cell invasion assay, and cellular traction force, we have demonstrated that cellular traction force can directly quantify the forces accountable for cell movement, to distinguish the antimetastatic drugs from the non-antimetastatic drugs.

Conclusion: Our findings indicate that cellular tractionforce is an invaluable tool for drug testing, particularly in the context of cancer metastasis.