SR-B1 uptake of HDL promotes prostate cancer proliferation and tumor progression

Traughber, C. A.; Opoku, E.; Brubaker, G.; Major, J.; Lu, H.; Lorkowski, S. W.; Neumann, C.; Hardaway, A.; Chung, Y.-M.; Gulshan, K.; Sharifi, N.; Brown, J. M.; Smith, J. D.

doi:10.1101/2020.02.24.963454

bioRxiv · 10.1101/2020.02.24.963454

SR-B1 uptake of HDL promotes prostate cancer proliferation and tumor progression

Traughber, C. A.·Opoku, E.·Brubaker, G.·Major, J.·Lu, H.·Lorkowski, S. W.·Neumann, C.·Hardaway, A.·Chung, Y.-M.·Gulshan, K.·Sharifi, N.·Brown, J. M.·Smith, J. D.

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Abstract

High density lipoprotein (HDL) metabolism, in part, is facilitated by scavenger receptor class B, type 1 (SR-B1) that mediates its uptake into cells. SR-B1 is upregulated in prostate cancer tissue. Here, we report that knockout (KO) of SR-B1 via CRISPR/Cas9 editing led to reduced HDL uptake into prostate cancer cells, and reduced their proliferation in response to HDL. In vivo studies using syngeneic SR-B1 wildtype (SR-B1+/+) and SR-B1 KO (SR-B1-/-) prostate cancer cells in WT and apolipoprotein-AI KO (apoA1-KO) C57BL/6J mice showed that WT hosts, containing higher levels of total and HDL-cholesterol, grew larger tumors than apoA1-KO hosts with lower levels of total and HDL-cholesterol. Furthermore, SR-B1-/- prostate cancer cells formed smaller tumors in WT hosts, than SR-B1+/+ cells in same host model. Tumor volume data was overall similar to survival data. We conclude that tumoral SR-B1 KO reduced HDL-mediated increases in prostate cancer cell proliferation and disease progression.

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Traughber, C. A., Opoku, E., Brubaker, G., Major, J., Lu, H., Lorkowski, S. W., Neumann, C., Hardaway, A., Chung, Y.-M., Gulshan, K., Sharifi, N., Brown, J. M., Smith, J. D.. 2020-02-26. SR-B1 uptake of HDL promotes prostate cancer proliferation and tumor progression. https://doi.org/10.1101/2020.02.24.963454

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