Type of Thesis
Ecology and Evolutionary Biology
Dr. Nancy Emery
Dr. Philip Owens
Dr. Barbara Demmig-Adams
Dispersal ecology offers a possible explanation for the behavior of prostate cancer (PCa), which disproportionately metastasizes to the bone. Organisms become more likely to leave their home patch when conditions are unfavorable, with the goal of becoming established in more favorable patches. Similarly, PCa cells are pushed from the prostate tumor by hypoxic stress and pulled toward the bone by the presence of bone stromal cells (BSCs), which support PCa growth and proliferation. When PCa settles in the bone, it leads to the formation of a feedforward loop in which PCa enhances osteoblast differentiation; osteoblasts in turn promote PCa proliferation via growth factors. This feedforward loop is mediated by bone morphogenetic proteins (BMPs), which drive bone growth by promoting osteoblast differentiation. In a further ecological parallel, this behavior appears analogous to parasitic manipulation of hosts. To test whether the feedforward loop could be disrupted, and to help determine the origin of the loop, I cultured PCa alone and in co-culture with BSCs with DorsoMorphin Homolog 1, an inhibitor of BMP. I found that monocultures of either PCa or BSCs were largely unaffected by DMH1. However, DMH1 treatment of the co-culture appeared to block excessive PCa proliferation but not osteoblast differentiation; at the same time, PCa, but not BSCs, upregulated BMP production, consistent with PCa driving the feedforward loop. These results suggest that DMH1 is a more effective treatment against metastatic prostate cancer than localized prostate cancer, and that the parasite analogy between cancer and bone cells is appropriate.
Oh, Matthew, "The Grass is Always Greener on the Other Side (of the Basement Membrane): Prostate Cancer Metastasis as Intracorporeal Dispersal" (2019). Undergraduate Honors Theses. 1794.