Glycocalyx mechanotransduction mechanisms are involved in renal cancer metastasis
| Autor: | Heriberto Moran, Limary M. Cancel, Peigen Huang, Sylvie Roberge, Tuoye Xu, John M. Tarbell, Lance L. Munn |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
SAHA
Suberoylanilide Hydroxamic Acid Histology Mechanotransduction QH301-705.5 Biophysics GAG Glycosaminoglycan HABP Hyaluronic Acid Binding Protein NDST1 N-Deacetylase N-Sulfotransferase 1 Cell Biology HAS1 Hyaluronan Synthase 1 HDAC Histone Deacetylase RHAMM Receptor for Hyaluronan Modulated Motility Glycocalyx Biochemistry Metastasis Renal carcinoma Genetics HA Hyaluronic Acid HS Heparan Sulfate HAS1−/− HAS1 knockout cell line Biology (General) Special Section on The Glycocalyx: Pathobiology and Repair Edited by Jillian Richter & Ralph Sanderson Molecular Biology eNOS Endothelial Nitric Oxide Synthase |
| Zdroj: | Matrix Biology Plus Matrix Biology Plus, Vol 13, Iss, Pp 100100-(2022) |
| ISSN: | 2590-0285 |
| Popis: | Highlights • Mechanotransduction through cell surface GAGs is a potential driver of metastasis. • SAHA, a histone deacetylase inhibitor, reduces tumor cell NDST1 and HS. • SAHA blocked metastasis of highly metastatic renal carcinoma cells in a mouse model. • Reduction of hyaluronic acid suppresses metastasis in a mouse kidney cancer model. Mammalian cells, including cancer cells, are covered by a surface layer containing cell bound proteoglycans, glycoproteins, associated glycosaminoglycans and bound proteins that is commonly referred to as the glycocalyx. Solid tumors also have a dynamic fluid microenvironment with elevated interstitial flow. In the present work we further investigate the hypothesis that interstitial flow is sensed by the tumor glycocalyx leading to activation of cell motility and metastasis. Using a highly metastatic renal carcinoma cell line (SN12L1) and its low metastatic counterpart (SN12C) we demonstrate in vitro that the small molecule Suberoylanilide Hydroxamic Acid (SAHA) inhibits the heparan sulfate synthesis enzyme N-deacetylase-N-sulfotransferase-1, reduces heparan sulfate in the glycocalyx and suppresses SN12L1 motility in response to interstitial flow. SN12L1 cells implanted in the kidney capsule of SCID mice formed large primary tumors and metastasized to distant organs, but when treated with SAHA metastases were not detected. In another set of experiments, the role of hyaluronic acid was investigated. Hyaluronan synthase 1, a critical enzyme in the synthetic pathway for hyaluronic acid, was knocked down in SN12L1 cells and in vitro experiments revealed inhibition of interstitial flow induced migration. Subsequently these cells were implanted in mouse kidneys and no distant metastases were detected. These findings suggest new therapeutic approaches to the treatment of kidney carcinoma metastasis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|