AI Article Synopsis

  • New treatment options are needed for high-grade serous carcinoma (HGSC), as it often spreads to the omentum and promotes tumor growth through angiogenesis.
  • Researchers investigated how cathepsin L (CathL) from HGSC affects the production of galectin-1 (Gal1) in human omental microvascular endothelial cells (HOMECs), which may play a role in tumor development.
  • The study found that CathL increases Gal1 synthesis, enhancing cell migration and proliferation in an autocrine manner, suggesting that targeting Gal1 could offer a new therapeutic approach in treating metastasized HGSC.

Article Abstract

Background: New treatment options for metastasised high-grade serous carcinoma (HGSC) are urgently needed. HGSC frequently metastasises to the omentum, inducing angiogenesis in the local omental microvasculature to facilitate tumour growth. We previously showed that HGSC-secreted cathepsin L (CathL) induces pro-angiogenic changes in disease relevant human omental microvascular endothelial cells (HOMECs), suggesting a role in tumour angiogenesis. Here we investigate whether CathL acts by inducing local production of the carbohydrate-binding protein galectin-1 (Gal1), which has been reported to be involved in tumourigenesis in other tumours.

Methods: HOMECs were used for all experiments. Gal1 mRNA and protein levels were measured by RT-PCR and ELISA respectively. Gal1-induced cell proliferation was assessed using WST-1 assay, migration using a transwell assay and in vivo Gal1 expression by immunohistochemistry.

Results: CathL transcriptionally regulated HOMEC production and secretion of Gal1 via activation of NFκB (significantly inhibited by sulfasalazine). Gal1 significantly enhanced HOMEC migration (p < 0.001) and proliferation (p < 0.001), suggesting an autocrine action. The latter was significantly reduced by the MEK/ERK1/2 inhibitors U0126 and PD98059 suggesting downstream activation of this pathway. Immunohistochemical analysis of omenta from HGSC patients with or without metastatic disease demonstrated a positive correlation between Gal1 expression and number of microvessels (r = 0.8702, p < 0.001), and area of vessels (r = 0.7283, p < 0.001), supporting a proangiogenic role for Gal1 in omental metastases.

Conclusion: HOMEC Gal1 transcription and release in response to CathL secreted from metastasising HGSC acts in an autocrine manner on the local microvasculature to induce pro-angiogenic changes, highlighting a potential new therapeutic target.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610868PMC
http://dx.doi.org/10.1186/s12967-019-1963-7DOI Listing

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