Marilyn L G Lamm

I have been interested in understanding the intricate signaling interactions among cancer cells, stromal cells, and the extracellular matrix environment that contribute to cancer progression, metastasis and the development of drug resistance. Our research has investigated reciprocal cross-talk in bone metastatic tumor development. We hypothesize a role for the Sonic hedgehog - Gli pathway in paracrine interactions between cancer cells and bone cells. Sonic hedgehog (Shh) is a member of the hedgehog family of ligands that activate an intracellular signaling cascade upon binding to transmembrane receptors (Patched) leading to transcriptional regulation of specific target genes by the Gli family of transcription factors. We have demonstrated that paracrine Shh-Gli signaling between prostate cancer cells and osteoblasts promote osteoblast differentiation, a hallmark of prostate cancer metastasis in bone. We have provided evidence that osteoblasts elaborate a different kind of collagen extracellular matrix in the presence of Shh-expressing prostate cancer cells. The structural properties of collagen matrix in bone microenvironment impact cancer cell functions. Knowledge from our research can inform our understanding of the role of the tumor fibrillar microenvironment, cancer cells and host stromal cells in carcinogenesis and metastasis.