Abstract
Gliomas are among the most lethal cancers, being highly resistant to both chemo- and radiotherapy. The expression of junctional adhesion molecule-A (JAM-A) was recently identified on the surface of stem cell-like brain tumor-initiating cells and suggested to function as a unique glioblastoma niche adhesion factor influencing the tumorigenic potential of brain tumor-initiating cells. We have recently identified high JAM-A expression to be associated with poor outcome in glioblastomas, and our aim was to further investigate the expression of JAM-A in gliomas focusing especially on the prognostic value in WHO grade II and III gliomas. JAM-A protein expression was evaluated by immunohistochemistry and advanced quantitative image analysis with continuous estimates of staining intensity. The JAM-A antibody stained tumor cell membranes and cytoplasm to various extent in different glioma subtypes, and the intensity was higher in glioblastomas than low-grade gliomas. We could not detect an association with overall survival in patients with grade II and III tumors. Double-immunofluorescence stainings in glioblastomas revealed co-expression of JAM-A with CD133, SOX2, nestin, and GFAP in tumor cells as well as some co-expression with the microglial/macrophage marker IBA-1. In conclusion, JAM-A expression was higher in glioblastomas compared to low-grade gliomas and co-localized with recognized stem cell markers suggesting an association of JAM-A with glioma aggressiveness. No significant association between JAM-A expression and overall survival was found in grade II and III gliomas. Further research is needed to determine the function and clinical impact of JAM-A in gliomas.
Highlights
Gliomas are the most frequent type of primary tumors in the central nervous system (CNS) [1]
Messenger RNA data from the National Cancer Institute REpository for Molecular BRAin Neoplastic Data (NCI REMBRANDT) suggested that high levels of junctional adhesion molecule-A (JAM-A) are associated with poor outcome in glioma patients, and we recently demonstrated that high JAM-A protein expression is associated with shorter survival in patients with GBM [14]
JAM-A was expressed in the cytoplasm and the membrane of tumor cells in all gliomas (Fig. 1d–i)
Summary
Gliomas are the most frequent type of primary tumors in the central nervous system (CNS) [1]. The aggressiveness of gliomas has been suggested to be associated with brain tumor-initiating cells (BTICs) that have the ability to self-renew and give rise to new tumors [2,3,4]. BTICs are relatively treatment-resistant and are thought to be located mainly in perivascular and hypoxic niches [5,6,7,8]. These niches may be maintained by adhesion molecules e.g., integrin-α6 and laminin-α2 [8, 9]. Using high-throughput flow cytometry screening, JAM-A has been found to be a glioblastoma (GBM)
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