Z Gastroenterol 2007; 45 - P037
DOI: 10.1055/s-2007-988184

The role of caveolin-1 in gastric cancer progression

E Burgermeister 1, X Xing 1, M Hiber 1, C Röcken 2, R Schmid 1, M Ebert 1
  • 1TU München, II. Medizinische Klinik, München, Germany
  • 2Charite, Institut für Pathologie, Berlin, Germany

Introduction: Caveolin-1 is a ˜20-kDa scaffold protein enriched in lipid rafts of the plasma membrane that interacts with pathogens and cellular receptors. Caveolin-1 functions as a tumor modulator in vivo by acting as a checkpoint for signaling cascades involved in cell growth and survival. However, the role of caveolin-1 in the stomach is unknown.

Methods: Expression of caveolin in human gastric cancer was assessed by immunohistochemistry and Western blot analyis. mRNA levels were assessed by quantitative PCR. Various functional assays were established to identify caveolin-dependent effects in gastric cancer cell lines.

Results: Immunohistochemistry of biopsies from gastric cancer (GC) patients (n=41) revealed that both the non-neoplastic mucosa and intestinal metaplastic epithelium expressed caveolin-1. However, GC cells of only three (7%) of 41 patients expressed caveolin-1 and were all of the intestinal type. Both caveolin-1 mRNA and protein levels were decreased in 14 (74%) of 19 and 7 (54%) of 13 GC patients compared to tumor-free tissue. Strong caveolin-1 reactivity was also found in the non-epithelial compartment (myocytes, fibroblasts, perineurium, endothelium) of both GC and tumor-free tissue and its frequency increased with the differentiation status of the tumor. In a series of human GC cells, caveolin-1 expression was low in cells derived from primary GC (AGS, SNU1) but positively correlated with the cell line's origin from distal metastases (N87, KATOIII, SNU5, MKN45, MKN7). Ectopic caveolin-1 slowed proliferation of adherent AGS cells but enhanced growth and survival in a soft agar matrix. Conversely, RNAi-knockdown of caveolin-1 in MKN45 accelerated cell growth independent of anchorage conditions.

Conclusions: These data indicate that loss of the growth inhibitory role of caveolin-1 in GC cells is an early event in gastric carcinogenesis and may contribute to its pathogenesis, while its late regain in metastatic cells may unfold its prosurvival function(s).