CHARACTERIZATION OF CANCER CELL-DISSOCIATION FACTOR IN A HIGHLY INVASIVE PANCREATIC-CANCER CELL-LINE

Background. Two pancreatic cancer cell lines, the highly invasive and metastatic cell line PC-1.0 and the weakly invasive and rarely metastatic cell line PC-1, were established from a pancreatic ductal carcinoma induced by N-nitrosobis (2-oxopropyl) amine in a Syrian golden hamster. Methods. The cancer cell dissociation activity in serum-free conditioned medium of PC-1.0 cells was partially purified using a heparin column, a hydroxylapatite column, anion exchange, and gel filtration high-performance liquid chromatography. Several biologic properties of the partially purified activity were evaluated. Results. Two cell lines exhibited different growth morphologic changes in vitro: the weakly invasive cell line PC-1 formed islandlike colonies, and the highly invasive cell line PC-1.0 grew mainly as single cells. The conditioned medium of PC-1.0 cells induced dissociation of islandlike colonies and morphologic changes of PC-1 cells to elongated cells, with a high frequency of pseudopodia formation similar to the morphologic findings of PC-1.0 cells. The dissociation activity did not bind to the heparin column and had an apparent molecular mass of >400 kDa, as deduced from gel filtration. Several immunoreactive proteinous bands were observed in immunoblotting analysis using a polyclonal blocking antibody. The partially purified activity enhanced cell motility, chemoinvasion, and cell adhesion to plastic plates and fibronectin. Conclusions. Highly invasive and metastatic PC-1.0 cells produce a soluble proteinous factor, called ''dissociation factor'' (DF), which induces cell dissociation of weakly invasive and rarely metastatic PC-1 cells. It seems likely that DF has a role in tumor invasion and metastasis.