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.

Podocalyxin is a marker of poor prognosis in colorectal cancer

“…The antigenic determinant of the polyclonal PODXL antibody is amino acid residues 278–415, whereas our antibody reacts with amino acid residues 189–192. One proposal is that distinct membranous PODXL expression, but not cytoplasmic expression, associates with poor prognosis in different cancers [17,25]. Interestingly, staining by our monoclonal antibody was mainly cytoplasmic in cancer cells, with no distinct membranous immunopositivity.…”

Podocalyxin-like and RNA-binding motif protein 3 are prognostic biomarkers in urothelial bladder cancer: a validatory study

“…High expression of PODXL, in particular in the membrane of tumour cells, has previously been demonstrated to correlate to an impaired prognosis in many major cancer forms like breast cancer [9], colorectal cancer [10–12], ovarian cancer [13], glioblastoma [14] and urothelial bladder cancer [15]. The results from this study further validate that membranous expression of PODXL is correlated to more aggressive tumours as it could not be demonstrated in non-invasive Ta-tumours.…”

“…Strong, in particular membranous, expression has been found to correlate with more aggressive tumours and poor survival in many cancer forms such as breast cancer [9], colorectal cancer [10–12], ovarian cancer [13], glioblastoma [14] as well as UBC [15]. In the latter study, we showed that PODXL is an independent risk factor for progressive disease and death in patients with all T-stages of UBC, as well as in the Ta/T1 subgroup.…”

PcMab-47: Novel Antihuman Podocalyxin Monoclonal Antibody for Immunohistochemistry

“…PODXL is known as a diagnostic marker and prognostic indicator in several cancers, including brain tumors, (6,16) prostate cancers, (17) testicular tumors, (2) renal cancers, (18) oral cancers, (19) thyroid cancers, (20) bladder cancers, (21) breast cancers, (22–24) ovarian cancers, (25) colorectal cancers, (26–29) pancreatic cancers, (30,31) and gastric cancers. (32) The glycans on PODXL bind to P-/E-/L-selectin expressed on platelets, endothelium, and leukocytes, respectively.…”