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.