Metastasis remains a leading cause of mortality for cancer patients. Disseminated tumor cells (DTCs) leave the original tumor to initiate the metastatic cascade. After successful navigation of the circulatory system, a subset of these DTCs then exits via capillaries at a distant site and infiltrate the tissue parenchyma. These DTCs colonize this new environment by poorly understood mechanisms involving adherence, remodeling, and proliferation. The objective of this proposal is to uncover the mechanisms by which a tumor cell can ectopically colonize a tissue that is both chemically and physically different from its original tissue. The genetic factors governing tissue tropism in cancer metastasis have been identified but the contributions of the dynamic interactions between tumor cells, and the microenvironment of the metastasizing cells are not well understood. Here we aim to understand the biophysical mechanisms by which these environmental changes occur, and whether such changes can be reversed or blocked.
| Blehm, Benjamin H; Devine, Alexus; Staunton, Jack R et al. (2016) In vivo tissue has non-linear rheological behavior distinct from 3D biomimetic hydrogels, as determined by AMOTIV microscopy. Biomaterials 83:66-78 |
| Tanner, Kandice; Gottesman, Michael M (2015) Beyond 3D culture models of cancer. Sci Transl Med 7:283ps9 |
| Blehm, Benjamin H; Jiang, Nancy; Kotobuki, Yorihisa et al. (2015) Deconstructing the role of the ECM microenvironment on drug efficacy targeting MAPK signaling in a pre-clinical platform for cutaneous melanoma. Biomaterials 56:129-39 |
