4 research outputs found
Stromal Endothelial Cells Directly Influence Cancer Progression
Cancer growth and metastasis are regulated in part by stromal cells such as fibroblasts and immune cells within the tumor microenvironment. Endothelial cells (ECs) are also ubiquitous within tumors because tumors are vascular, and yet, the impact of tumor-resident ECs is less well understood. Through paracrine regulation, ECs modulate a diverse spectrum of pathophysiologic processes in normal and hyperplastic tissues. We hypothesized that ECs offer similar paracrine regulatory control of cancer biology. Indeed, secretions from quiescent ECs muted the proliferative and invasive phenotype of lung and breast cancer cells in vitro and reduced cancer cell protumorigenic and proinflammatory signaling. EC perlecan silencing significantly changed this regulatory relationship, eliminating the ability of ECs to inhibit cancer cell invasiveness via increased interleukin-6 secretion. Moreover, implanting ECs embedded within porous matrices slowed adjacent xenograft tumor growth and prevented architectural degeneration, with a concomitant reduction in proliferative and tumorigenic markers. Finally, lung carcinoma cells pretreated with intact EC-conditioned media, but not media conditioned with perlecan-silenced ECs, exhibited reduced micrometastatic burden after tail vein injection. These findings add to an emerging appreciation of EC-regulatory effects that transcend their structural roles and pave the way for improved characterization and control of EC-cancer cross-talk interactions for diagnosis, prognosis, and treatment of cancer.National Institutes of Health (U.S.) (grant R01 GM49039)National Institutes of Health (U.S.) (Medical Scientist Training Program Fund)American Heart Association (Scientist Development grant 2630129)National Institutes of Health (U.S.) (1K08DK080946)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (1K08DK080946)National Kidney Foundation (Young Investigatory Grant Award
Expression of syndecan-1 and cathepsins D and K in advanced esophageal squamous cell carcinoma.
The key features of malignant neoplasms are their local invasiveness and metastatic potential. Syndecan-1 - integral membrane heparan sulfate proteoglycan and cathepsins D and K - lysosomal proteases are important factors influencing different aspects of these processes. The study was undertaken to determine their expression in esophageal squamous cell carcinoma, and analyze relationship to selected clinicopathological features as well as to survival. Formalin-fixed, paraffin-embedded sections from 39 advanced esophageal squamous cell carcinoma were used for immunohistochemical staining. The epithelial and stromal staining were evaluated separately and compared to conventional clinicopathological features and one-year survival. Positive epithelial immunostaining for syndecan-1, cathepsin D and K were observed in 82.05%, 56.41% and 30.77% of tumors, respectively. However, stromal staining was noted in 51.28%, 51.28% and 46.15% ones, respectively. Epithelial syndecan-1-positive cases were significantly more frequent in well- and moderately differentiated carcinomas. Stromal cathepsin D expression predominated in tumors with infiltrative growth pattern. However, there were no statistically significant differences between any marker-positive and -negative groups with respect to other clinicopathological features studied. The only factors significantly influencing one-year survival were epithelial cathepsin D staining and distant metastasis. In a group of patients who survived one year post surgery, the percentage of cases with negative epithelial cathepsin D staining and without features of distant metastasis were higher. The results may suggest a relationship between syndecan-1 and cathepsins D and K with growth and invasiveness of esophageal squamous cell carcinoma, but such thesis requires further study on a larger and more heterogeneous population