Metastasis from the tumor interior and necrotic core formation are regulated by breast cancer-derived angiopoietin-like 7.

Necrosis in the tumor interior is a common feature of aggressive cancers that is associated with poor clinical prognosis and the development of metastasis. How the necrotic core promotes metastasis remains unclear. Here, we report that emergence of necrosis inside the tumor is correlated temporally with increased tumor dissemination in a rat breast cancer model and in human breast cancer patients. By performing spatially focused transcriptional profiling, we identified angiopoietin-like 7 (Angptl7) as a tumor-specific factor localized to the perinecrotic zone. Functional studies showed that Angptl7 loss normalizes central necrosis, perinecrotic dilated vessels, metastasis, and reduces circulating tumor cell counts to nearly zero. Mechanistically, Angptl7 promotes vascular permeability and supports vascular remodeling in the perinecrotic zone. Taken together, these findings show that breast tumors actively produce factors controlling central necrosis formation and metastatic dissemination from the tumor core.

[Semaphorin 6D and Snail are highly expressed in gastric cancer and positively correlated with malignant clinicopathological indexes].

Objective To investigate the expression of semaphorin 6D (SEMA6D) and Snail and their clinicopathological implications in gastric cancer. Methods 54 cases of gastric cancer tissues and 26 paracancerous gastric mucosa were collected for detecting the expression of SEMA6D and Snail by immunohistochemistry and Western blot analysis. The co-localization of SEMA6D and Snail was observed by immunofluorescence double staining and laser scanning confocal microscopy. The correlation between SEMA6D and Snail and their relationships with the clinicopathological features of the patients were analyzed. Results Compared with the paracancerous gastric mucosa, the protein expression of SEMA6D and Snail in the gastric cancer significantly increased, and there was a significant co-localization of SEMA6D and Snail in gastric cancer. Further statistical analysis showed that the expression of SEMA6D and Snail in gastric cancer was positively correlated with the degree of differentiation, invasion, lymph node metastasis and TNM stage. Conclusion The high expression of SEMA6D and Snail in gastric cancer are related to the malignant clinicopathological indexes of gastric cancer.