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Role of hyaluronan turnover in tumor cell motility and vesicle trafficking
Enhanced turnover of hyaluronan (HA) via co-overexpression of its synthesis (HAS3) and degradation (Hyal1) enzymes has been shown to enhance prostate tumor cell proliferation and migration. Injection of these cells into a mouse model induces increased tumorigenesis and metastasis to the lymph nodes. It is of interest to elucidate the mechanisms behind these physiological changes to develop better treatments for aggressive prostate cancer. We determined that 22Rv1 Hyal1 cells have an increased rate of cell cycling compared to poorly-tumorigenic 22Rv1 HAS3 cells. 22Rv1 HAS3 cells also exhibited a lower expression of N-cadherin on the cell surface. Overexpression of Hyal1 increased the global endocytic rate of the cell. Hyal1 was trafficked into endocytic vesicles, a portion being identified as lysosomes, and this was dependent on its catalytic activity. Inhibition of endosomal trafficking pathways revealed that internalized Hyal1 does not undergo ER to Golgi transport in its normal trafficking, but is involved in autophagosome/lysosome fusion and inhibition of lysosomal acidification caused buildup of Hyal1. Hyal1 is also present in exosomes released by 22Rv1 Hyal1 tumor cells. Presence of wild type Hyal1 associated with exosomes, not increased concentration of exosomes, stimulated migration in exosome-treated prostate stromal cells. These results reveal multiple mechanisms by which Hyal1 could be supporting the progression of prostate cancer. ^
Chemistry, Biochemistry|Health Sciences, Oncology
McAtee, Caitlin O, "Role of hyaluronan turnover in tumor cell motility and vesicle trafficking" (2014). ETD collection for University of Nebraska - Lincoln. AAI3618782.