This week’s Biology Seminar is titled “Perivascular MSCs and the basement Membrane Roles in Bone Metastasis” by Research Associate Professor in the Skeletal Research Center and Director of the Cell Culture Facility Dr. Rodrigo Somoza Palacios.

The skeleton is a preferred organ for cancer dissemination from various tumor malignancies. Our objective is to understand the function of the Bone Marrow microenvironment, and specifically of its perivascular components, in the establishment of skeletal metastasis. Our studies aim to test the innovative hypothesis that Mesenchymal Stem Cells (MSCs), as perivascular cells (pMSCs), function as gatekeepers controlling tumor cell invasion to bone. This new hypothesis provides clinically relevant information for therapeutic strategies that innovatively aim at reducing the engraftment of circulating cancer cells by closing the gate through which the metastatic cell transit into the normal bone. We propose that the inhibition of one or combination of tumor cells and pMSCs specific genes would prevent or attenuate the metastatic process in vivo. To experimentally dissect the various cellular and extracellular matrix components controlling extravasation, we have designed and validated a unique in vivo extraskeletal humanized bone marrow niche-mimicking platform (humanized Ossicle). This platform is centered around the use of a porous, calcium phosphate ceramic into which human bone marrow-derived MSCs (hBM-MSC) are loaded and then implanted into the back of immune deficient mice. Bone is fabricated onto the walls of the ceramic by hBM-MSCs anchored at these locations and, at the centers; the host-derived blood vessels have pMSCs within the marrow space. We have documented that when melanoma is injected into the bloodstream of the mouse, the bones become black (melanin), as is the bone in habitat. If we manipulate the expression of molecules involved in the process, such as CXCL12 or MCAM in the pMSCs, the mouse bone is black and the habitat is white. This black-and-white result sets the stage to dissect the participation of pMSCs and the perivascular basement membrane in driving Skeletal Metastasis. In addition to the significant direct clinical impact, this work is expected also to provide the platform for future projects addressing the roles of pMSCs that may influence other skeletal metastasis, such as regulation of local antitumor immune response, cancer cells dormancy and tumor angiogenesis, and to serve as template for the study of other osteotropic malignancies (prostate and lung cancer).

Please join us on the 3rd floor of DeGrace hall at 3:45pm for coffee and snacks before the seminar!

This seminar will be available on Zoom.