CSB327 Lecture 16 Summary

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Cell and Systems Biology
Maurice Ringuette

Lecture 16 - The stroma plays a critical role in cancer progression - Peritoneal metastasis is distinct from hematological (blood-borne) metastasis - Hematological (blood-borne) metastasis is a multi-step and inefficient process - Peritoneal metastasis o Shared by ovarian cancer and gastrointestinal tract cancer o Localized within the abdominal cavity o Primary site of tumour formation (not the cause of death)  From ovary or fallopian tube epithelia  From gastrointestinal cancers that have invaded through the peritoneal membrane  From surgical perforation o Cancer cells exfoliate into peritoneal fluid and spread locally to secondary sites (cause of death) o Poor prognosis  Diagnosed at late stage after peritoneal metastasis  Surgery is ineffective once spread  Chemoresistant disease is common  Peritoneal metastasis proceeds rapidly o Peritoneal membrane structure  Single layer of mesothelial cells with underlying ECM (e.g., FN, CI, CIV, LM)  Covers the vast surface of abdominal cavities and visceral organs o Inhibited by mesothelial cells  Two mechanisms  Secrete HA and proteoglycans o Provides anti-adhesive peritoneal surface o Promotes gliding  Conceal collagen I matrix (stroma) o Prevents cancer cell attachment o Collagen I is the preferred substratum for ovarian cancer cell attachment and migration o Initial dissemination to milky spots  Drainage portals (lymphatic ducts) for peritoneal fluid where mesothelium is disrupted  Underlying ECM (e.g., rich in collagen I) is exposed  Mesothelial cells surrounding milky spots have rounded morphology that further expose the collagen ECM  Omentum is covered with milky spots and therefore, a preferential site for tumour cell attachment  Metastasis only in omentum initially  Ascites fluid begins to accumulate by the inflammatory response  Widespread metastasis o Massive seeding on the peritoneal wall and visceral organs o Enhanced by inflammation  Inflammatory cytokines released by macrophages promote rapid and efficient spreading with
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