Intriguingly, certain epithelial cancers can be induced to regenerate normal GSK2269557 (free base) tissue morphology when presented with embryonic mesenchyme or exogenous ECM scaffolds. The upregulation of ECM genes has not only been detected in tumors, but has also been associated with poor prognosis. In addition, cancer progression is characterized by extensive matrix remodeling and progressive 1235034-55-5 biological activity stiffening of the stroma, which affects epithelial-stromal interactions, that could inturn enhance epithelial cell growth, affect breast tissue organization, and promote cell invasion and survival. While the ECM in the normal breast is soft, the increased rigidity of the matrix, characteristic of malignant transformation, or externally applied force, stimulated proliferation and promoted a tumor-like behavior in mammary cells. Furthermore, altered expression of a6-integrins has been reported in breast cancer cells. In this study, we demonstrated a differential rigidity response in the single cell populations derived from a highly invasive breast cancer cell line MDA-MB231. These SCPs displayed differential metastatic potential and tissue tropism in vivo, which were correlated with different patterns of gene expression. Based on these profiles, SCPs displayed clustering in three groups that corresponded to their metastatic potential: bone, lung, or nonmetastatic group. A few of these lines were also reported to cause adrenal gland metastases. Due to the intrinsic limitation of the animal model, no lines specifically targeting the brain or regional lymph nodes were isolated. As expected, different SCP clusters showed differential rigidity responses on both collagen and fibronectin. While soft collagen matrices promoted proliferation of the lung-targeting and non-metastatic SCPs, rigid matrices inhibited growth of lungtargeting and non-metastatic lines, while promoting proliferation of bone-targeting SCPs. The effect of FN rigidity was even more pronounced, since most lines did not proliferate on FN-coated matrices, except bone-targeting lines that grew rapidly on rigid FN-coated gels. This observation can be correlated with the differences in the rigidity of the target tissues, which
