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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011559-05
Application #
9779959
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
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