SR-B1 uptake of HDL promotes prostate cancer proliferation and tumor progression
| Autor: | Jonathan D. Smith, Jennifer Major, Aimalie Hardaway, Kailash Gulshan, Emmanuel Opoku, Gregory Brubaker, Nima Sharifi, C. Alicia Traughber, Hanxu Lu, Yoon-Mi Chung, Shuhui Wang Lorkowski, Chase K.A. Neumann, J. Mark Brown |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Chemistry Wild type Metabolism medicine.disease 3. Good health 03 medical and health sciences Prostate cancer chemistry.chemical_compound 0302 clinical medicine High-density lipoprotein Downregulation and upregulation In vivo Tumor progression 030220 oncology & carcinogenesis medicine Cancer research lipids (amino acids peptides and proteins) Scavenger receptor 030304 developmental biology |
| Popis: | 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 vivostudies 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|