Heparan sulfate proteoglycans mediate renal carcinoma metastasis
| Autor: | Jonathan W. Song, Ye Zeng, Lance L. Munn, Peigen Huang, Limary M. Cancel, John M. Tarbell, Sylvie Roberge, Zhong-Dong Shi, Henry Qazi |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Pathology medicine.medical_specialty Gene knockdown Heparan sulfate Biology medicine.disease In vitro Metastasis Glycocalyx 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Oncology Downregulation and upregulation Proteoglycan chemistry Tumor progression Cancer research biology.protein medicine |
| Zdroj: | International Journal of Cancer. 139:2791-2801 |
| ISSN: | 0020-7136 |
| Popis: | The surface proteoglycan/glycoprotein layer (glycocalyx) on tumor cells has been associated with cellular functions that can potentially enable invasion and metastasis. In addition, aggressive tumor cells with high metastatic potential have enhanced invasion rates in response to interstitial flow stimuli in vitro. Our previous studies suggest that heparan sulfate (HS) in the glycocalyx plays an important role in this flow mediated mechanostransduction and upregulation of invasive and metastatic potential. In this study, highly metastatic renal cell carcinoma cells were genetically modified to suppress HS production by knocking down its synthetic enzyme NDST1. Using modified Boyden chamber and microfluidic assays, we show that flow-enhanced invasion is suppressed in HS deficient cells. To assess the ability of these cells to metastasize in vivo, parental or knockdown cells expressing fluorescence reporters were injected into kidney capsules in SCID mice. Histological analysis confirmed that there was a large reduction (95%) in metastasis to distant organs by tumors formed from the NDST1 knockdown cells compared to control cells with intact HS. The ability of these cells to invade surrounding tissue was also impaired. The substantial inhibition of metastasis and invasion upon reduction of HS suggests an active role for the tumor cell glycocalyx in tumor progression. |
| Databáze: | OpenAIRE |
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