DEFINING THE INVASIVE PHENOTYPE OF PROXIMAL GASTRIC-CANCER CELLS

Background. Adenocarcinoma of the proximal stomach is now the most rap idly rising cancer among men in the United States. The development of metastases is the major cause of morbidity and mortality for this aggr essive disease. The mechanisms by which tumor cells invade the basemen t membrane are unknown for this disease. We have identified and establ ished 5 invasive and noninvasive adenocarcinoma cell lines arising fro m the proximal stomach, which can be used to examine the mechanisms in volved in tumor cell invasion. Methods. The expression of factors asso ciated with tumor cell attachment, proteolysis, and inhibition of prot eolysis was determined by reverse transcription of mRNA to cDNA and su bsequent amplification by the polymerase chain reaction. In addition, cells were examined for morphologic changes by scanning electron micro scopy. Results. Invasive proximal gastric cancer cells express the 72- kD form of collagenase type IV, whereas the noninvasive cells do not. Other factors examined (including the laminin receptor, cathepsin B, c athepsin L, urokinase-type plasminogen activator, and tissue inhibitor metalloproteinases) are expressed by both invasive and noninvasive ga stric cancer cells, whereas collagenase type IV 92-kD form is not expr essed by any of the cells examined. In addition, scanning electron mic roscopy revealed that all the invasive cell lines exhibit long cytopla smic extensions. The noninvasive cells express short cytoplasmic proje ctions and are rounder than the invasive proximal gastric cancer cell lines.