In collaboration with the team of Professor Raquel Seruca, from IPATIMUP, we have identified a new surface marker for gastric cancer cells. This discovery may allow the development of new technologies leading to diagnosis of gastric cancer sub-types (still without efficient diagnosis available) or even to specific therapies, with the ultimate goal of not affecting normal cells, thus minimizing the undesirable side effects of present therapies.
da Cunha CB, Oliveira C, Wen X, Gomes B, Sousa S, Suriano G, Grellier M, Huntsman DG, Carneiro F, Granja PL, Seruca R. De novo expression of CD44 variants in sporadic and hereditary gastric cancer. Laboratory Investigation 2010; In Press.
CD44 is the major ubiquitously expressed cell surface receptor for hyaluronate. The CD44 gene encodes several protein isoforms due to extensive alternative splicing and post-translational modifications. Some of these CD44 variable isoforms have been foreseen as key players in malignant transformation and their expression is highly restricted and highly specific, unlike the canonical CD44 standard isoform. In this study, we aimed at dissecting the mRNA splicing pattern of CD44 in normal stomach and gastric cancer (GC) cell lines (n=9) using cloning and quantitative mRNA amplification assays. Moreover, we assessed the RNA levels and protein expression pattern of relevant splicing forms in distinct premalignant and malignant gastric lesions (sporadic (n=43) and hereditary (n=3) forms) using real-time RT-PCR and immunohistochemistry. We also explored the association of CD44 and E-cadherin expression by immunohistochemistry, as E-cadherin has a pivotal functional role in GC. We established the pattern of CD44 variant forms in normal stomach and gastric malignancy. We observed that although exon v6-containing isoforms were rarely expressed in normal gastric mucosa, they became increasingly expressed both in gastric premalignant (hyperplastic polyps, complete and incomplete intestinal metaplasia, low- and high-grade dysplasia) and malignant lesions (cell lines derived from GCs, primary sporadic GCs and hereditary diffuse GCs (HDGCs)). Moreover, we verified that whenever E-cadherin expression was absent, exon v6-containing CD44 isoforms were overexpressed. The lack of expression of CD44 isoforms containing exon v6 in the surface and foveolar epithelia of normal stomach and, its de novo expression in premalignant, as well as in sporadic and hereditary malignant lesions of the stomach, pinpoint CD44 v6-containg isoforms as potential biomarkers for early transformation of the gastric mucosa. Further, our results raise the hypothesis of using CD44v6 as a marker of early invasive intramucosal carcinoma in HDGC CDH1 mutation carriers that lack CDH1 expression in their tumors.
Specific marker for gastric cancer discovered. In Publico (only in Portuguese). Oct 2010
Discovery of marker for gastric cancer unlocks new therapies. In Ciencia Hoje (only in Portuguese). Oct 2010