Glycocalyx mechanotransduction mechanisms are involved in renal cancer metastasis

Heriberto Moran; Limary M. Cancel; Peigen Huang; Sylvie Roberge; Tuoye Xu; John M. Tarbell; Lance L. Munn

Matrix Biology Plus (Feb 2022)

Glycocalyx mechanotransduction mechanisms are involved in renal cancer metastasis

Heriberto Moran,
Limary M. Cancel,
Peigen Huang,
Sylvie Roberge,
Tuoye Xu,
John M. Tarbell,
Lance L. Munn

Affiliations

Heriberto Moran: Wallace H. Coulter Laboratory, Department of Biomedical Engineering, The City College of New York, The City University of New York, New York, NY 10032, USA
Limary M. Cancel: Wallace H. Coulter Laboratory, Department of Biomedical Engineering, The City College of New York, The City University of New York, New York, NY 10032, USA
Peigen Huang: Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
Sylvie Roberge: Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
Tuoye Xu: Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
John M. Tarbell: Wallace H. Coulter Laboratory, Department of Biomedical Engineering, The City College of New York, The City University of New York, New York, NY 10032, USA; Corresponding authors at: Department of Biomedical Engineering, The City College of New York, 160 Convent Ave, New York, NY 10031, USA.
Lance L. Munn: Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Corresponding authors at: Department of Biomedical Engineering, The City College of New York, 160 Convent Ave, New York, NY 10031, USA.

Journal volume & issue: Vol. 13
p. 100100

Abstract

Read online

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.

Published in Matrix Biology Plus

ISSN: 2590-0285 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: https://www.journals.elsevier.com/matrix-biology-plus

About the journal

Abstract

Keywords