Achievement

Cancer deaths are primarily caused by metastases, not by the parent tumor. During metastasis, malignant cells detach from the parent tumor, and spread through the circulatory system to new tissues and organs. The physical-chemical mechanisms within the cellular microenvironment that initiate the onset of metastasis are not well understood. We recently discovered that human colon carcinoma cells exhibit a dissociative, metastasis-like phenotype in vitro when cultured on substrates with appropriate mechanical stiffness (21 kPa- 47 kPa). The cell-cell adhesion molecule E-Cadherin, a metastasis hallmark, decreases 3-5 fold on cell membranes in concert with disassociation. Real-time PCR analysis shows an up-regulation of metastasis marker by 20 times. Thus, these HCT-8 cells undergo a stable cell-state transition with increased metastatic characteristics. This finding suggests that the onset of metastasis may be fundamentally linked to the mechanical microenvironment of the tumor.