Accession Number : ADA609384


Title :   CTC-Endothelial Cell Interactions during Metastasis


Descriptive Note : Annual rept. 1 Apr 2012-31 Mar 2014


Corporate Author : CORNELL UNIV MEDICAL COLL (WEILL) NEW YORK


Personal Author(s) : Gakhar, Gunjan


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a609384.pdf


Report Date : Jun 2014


Pagination or Media Count : 44


Abstract : Hematogenous metastasis accounts for the majority of cancer-related deaths, yet the mechanism remains unclear. Circulating tumor cells (CTCs) in blood may employ different pathways to cross blood endothelial barrier and establish a metastatic niche. Several studies provide evidence that prostate cancer (PCa) cell tethering and rolling on microvascular endothelium via Eselectin/ E-selectin ligand interactions under shear flow theoretically promote extravasation and contribute to the development of metastases. However, it is unknown if CTCs from PCa patients interact with E-selectin expressed on endothelium, initiating a route for tumor metastases. Here we report that CTCs derived from PCa patients showed interactions with E-selectin and Eselectin expressing endothelial cells. To examine E-selectin-mediated interactions of PCa cell lines and CTCs derived from metastatic PCa patients, we used fluorescently-labeled anti-prostate specific membrane antigen (PSMA) monoclonal antibody J591-488 which is internalized following cell-surface binding. We employed a microscale flow device consisting of E-selectin-coated microtubes and human umbilical vein endothelial cells (HUVECs) on parallel-plate flow chamber simulating vascular endothelium. We observed that J591-488 did not significantly alter the rolling behavior in PCa cells at shear stresses below 3 dyn/cm2. CTCs obtained from 31 PCa patient samples showed that CTCs tether and stably interact with E-selectin and Eselectin expressing HUVECs at physiological shear stress. Interestingly, samples collected during disease progression demonstrated significantly more CTC/E-selectin interactions than samples during times of therapeutic response (p=0.016). Analysis of the expression of sialyl Lewis X (sLex) in patient samples showed that a small subset comprising 1.9-18.8% of CTCs possess high sLex expression.


Descriptors :   *CELLS(BIOLOGY) , *METASTASIS , ANTIGENS , ENDOTHELIUM , LIGANDS , MONOCLONAL ANTIBODIES , NEOPLASMS , PROSTATE CANCER


Subject Categories : Biology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE