The anti-adhesive mucin podocalyxin may help initiate the transperitoneal metastasis of high grade serous ovarian carcinoma.

Abstract

High grade serous ovarian tumors often metastasize transperitoneally, a process that begins when small tumor nodules de-adhere and are released into the fluid of the abdominal cavity where they float freely to reach new sites on the peritoneal wall. Podocalyxin, a small anti-adhesive sialomucin, has been shown to contribute to non-adhesive membrane domain formation in some epithelia and is overexpressed in a variety of cancers. We therefore assessed podocalyxin expression on a previously characterized tissue microarray and found that 87% (169/194) of high grade serous epithelial ovarian carcinomas were positive for podocalyxin. In addition, cell surface localization of podocalyxin was associated with a significant decrease in disease-free survival in these tumors. When podocalyxin was force-expressed in serous ovarian carcinoma-derived OVCAR-3 cells it was targeted to the cell surface and it decreased the adhesion of these cells to mesothelial monolayers, fibronectin and immobilized β1 integrin-binding antibodies. This decrease in adhesion was associated with a modest decrease in cell surface β1 integrin. In monolayer culture, podocalyxin was targeted to the free, apical domains of OVCAR-3 cells and it appeared to decrease β1 integrin levels on the attached basolateral domains of the same cells. Furthermore, in 3-dimensional basement membrane gel culture, the cells formed small, cohesive nodules and podocalyxin localized to membrane domains at the cell-basement membrane interface. Therefore, podocalyxin's ability to facilitate the formation of non-adhesive membrane domains may contribute to the formation of free-floating high grade serous tumor nodules during the initial steps of transperitoneal metastasis.

• Authors: Jane A Cipollone, Marcia L Graves, Martin Köbel, Steve E Kalloger, Tak Poon, C Blake Gilks, Kelly M McNagny, Calvin D Roskelley
• Journal: Clinical & experimental metastasis (Clin Exp Metastasis) Vol. 29 Issue 3 Pg. 239-52 (Mar 2012) ISSN: 1573-7276 [Electronic] Netherlands
• PMID: 22262060 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Integrin beta1
• Sialoglycoproteins
• podocalyxin

Topics

• Cell Adhesion
• Cell Line, Tumor
• Cystadenoma, Serous (pathology)
• Endometrium (chemistry)
• Fallopian Tubes (chemistry)
• Female
• Humans
• Integrin beta1 (analysis)
• Ovarian Neoplasms (pathology)
• Ovary (chemistry)
• Peritoneal Neoplasms (secondary)
• Sialoglycoproteins (analysis, physiology)