Is mucin a determinant of peritoneal dissemination of gastrointestinal cancer? Analysis of mucin depletion in two preclinical models

Background. Mucinous gastrointestinal cancers may indicate a higher propensity for widespread peritoneal seeding than their non-mucinous counterparts. We hypothesized that mucin content of gastrointestinal cancer cells and tumors is an indicator of cell viability and a determinant of the peritoneal tumor burden and tested our hypothesis in relevant experimental models. Methods. MKN45 and LS174T models of human gastrointestinal cancer were treated with known mucin-depleting agents in vitro and in vivo, their mucin production was evaluated with Western blot immunohistochemistry, PAS staining and ELISA, and its correlation with cell viability and peritoneal tumor burden was analyzed. Results. A relationship was found between the viability of cancer cells and their mucin levels in vitro. In agreement, when treated animal models were categorized into low- and high-burden groups (based on the weight and number of the peritoneal nodules), tumoral mucin levels were found to be significantly higher in the latter group. Conclusions. Tumoral mucin is apparently among the factors that dictate the pattern and extent of the peritoneal spread of gastrointestinal cancer, where it allows for enhanced dissemination and redistribution. If further tested and validated, our hypothesis could lay the basis for the development of novel mucin-targeted strategies (AU)

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Is mucin a determinant of peritoneal dissemination of gastrointestinal cancer? Analysis of mucin depletion in two preclinical models.

BACKGROUND: Mucinous gastrointestinal cancers may indicate a higher propensity for widespread peritoneal seeding than their non-mucinous counterparts. We hypothesized that mucin content of gastrointestinal cancer cells and tumors is an indicator of cell viability and a determinant of the peritoneal tumor burden and tested our hypothesis in relevant experimental models. METHODS: MKN45 and LS174T models of human gastrointestinal cancer were treated with known mucin-depleting agents in vitro and in vivo, their mucin production was evaluated with Western blot immunohistochemistry, PAS staining and ELISA, and its correlation with cell viability and peritoneal tumor burden was analyzed. RESULTS: A relationship was found between the viability of cancer cells and their mucin levels in vitro. In agreement, when treated animal models were categorized into low- and high-burden groups (based on the weight and number of the peritoneal nodules), tumoral mucin levels were found to be significantly higher in the latter group. CONCLUSIONS: Tumoral mucin is apparently among the factors that dictate the pattern and extent of the peritoneal spread of gastrointestinal cancer, where it allows for enhanced dissemination and redistribution. If further tested and validated, our hypothesis could lay the basis for the development of novel mucin-targeted strategies.

The critical role of vascular endothelial growth factor in tumor angiogenesis.

Angiogenesis is the formation of new blood vessels from the pre-existing vasculature. Besides its role in normal physiology, angiogenesis is significantly involved in many pathological conditions, including inflammation, cardiovascular diseases and cancer. Numerous studies have been undertaken in the area of tumor angiogenesis. It is known that pathological angiogenesis is necessary for tumors to proceed from avascular, dormant stage to vascular, sprouting stage and also contributes to their later invasion and metastasis. Playing a central role in tumor angiogenesis, vascular endothelial growth factor is considered as a key target in therapeutic approaches. This article aims to review the critical role of VEGF in tumor angiogenesis and the importance of VEGF-targeted strategies in cancer treatment.