The production of carcino-embryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were investigated in 28 clones isolated from a human pancreatic cancer cell line (SUIT-2) and related to in vitro morphology of the clones and in vivo tumorigenicity. Clones of fusiform and polygonal cells could be morphologically distinguished in confluent cultures. There was no significant difference in CEA production between fusiform-cell clones (2.10 +/- 2.70 ng/L x 10(6) per 24 h) and polygonal-cell clones (6.01 +/- 7.30 ng/L x 10(6) per 24 h), but polygonal-cell clones had higher production of CA19-9 (1176.1 +/- 1628.4 U/L x 10(6) per 24 h) than fusiform (6.0 +/- 7.3 U/L x 10(6) per 24 h; P < 0.01). Production of CA19-9 in vitro correlated with the histological grade of differentiation in vivo in nude mice (r = 0.73, P < 0.001), but CEA production did not. The polygonal-cell clones developed well-differentiated carcinomas in vivo and produced significantly more CA19-9 (P < 0.001) than fusiform-cell clones, which generally developed into poorly differentiated tubular adenocarcinomas in vivo. This cell line may provide an appropriate system for further studies of the biology and therapy of pancreatic cancer.

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Adenocarcinoma in the anal canal associated with an anal fistula is extremely rare, and in most cases its origin is difficult to ascertain because the primary sites have already been destroyed before any diagnosis of malignancy is able to be made. We report herein the case of a 62-year-old man found to have papillary adenocarcinoma with partial mucinous carcinoma associated with an anal fistula. The tumor was not exposed to the mucosal surface of the anal canal or rectum and an abdominoperineal resection was carried out. Macroscopic findings suggested that the tumor had developed from the anal fistula; however, the tumor showed a positive results when tested for O-acetylated sialic acids. This test also proved positive in the mucus of normal rectal mucosa, but not in the mucus of the anal glands. We speculated that the results of these tests may indicate that this tumor could have originated from the rectal mucosa, from where it migrated into the anal fistula.

Cell lines with high metastatic capacity to the lung were established by sequential passage of a human pancreatic cancer cell line (SUIT-2) through the lung of a nude mouse, via the lateral tail vein and from a subcutaneous inoculum. Cells of the parental SUIT-2 and sublines S2-VPx (x-cycle selection from SUIT-2 cells, by Vein-Pulmonary metastasis-culture) and S2-CPx (x-cycle selection, by Cutis-Pulmonary metastasis-culture) were injected intravenously or subcutaneously into nude mice to produce experimental or spontaneous lung metastasis. The S2-VP10 cell line produced pulmonary metastases in 100% of the nude mice, when injected intravenously. It failed, however, to produce more lung colonies than its parent cell line, when injected subcutaneously. The S2-CP8 cell line produced extensive pulmonary metastases in 100% of the nude mice, when injected either intravenously or subcutaneously. This study indicates that the nude mouse provided a good model for in vivo selection of metastatic cells from SUIT-2 cells both experimentally and spontaneously, and that the SUIT-2, S2-VPx, and S2-CPx cell lines will be valuable in the study of human cancer metastasis. We previously reported high levels of ezrin expression in the S2-VP10 and S2-CP8 cell lines. Here we show that these cell lines exhibit a greater capacity to invade or attach to various extracellular matrix components than the parent SUIT-2 cells. The S2-CP8 cell lines also exhibit greater level of type-I and type-IV collagen-degrading activity than the parent SUIT-2 cell line and the S2-VP10 cell line, which shows similar collagen-degrading activity to the parent SUIT-2 cells. In RT-PCR studies, SUIT-2, S2-CP8 and S2-VP10 cell lines constitutively expressed many matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP7, MMP-9, MMP-10 and MMP-14). These results suggest that some parameters that enhance adhesion and invasion are important to both experimental and spontaneous metastasis and the collagen degrading enzymes are predicted to play a key-role during spontaneous metastasis.

The present study extends our investigations into the metastatic heterogeneity among four clonal cell lines (S2-007:H, S2-013:M1, S2-020:M2, and S2-028:L) from a human pancreatic cancer cell line (SUIT-2), and extends our discussion the positive correlation between metastatic potential and the type I collagenase activity of the cells, focusing on their interaction with extracellular matrix. Ability to attach to the reconstituted basement membrane (Matrigel) was higher for clone H than clone L during an observation period of 30-60 min, whereas clones M1 and M2 were found to be intermediate in ability. In densitometric and radioactive studies, clone L exhibited the lowest collagenolytic activity against mouse and human type IV collagen, while clone H exhibited the highest activity in the densitometric study and clone M1 was the highest in the radioactive study. The production of urinary-type plasminogen activator was highest in clone L and lowest in clone H. On the other hand, tissue-type plasminogen activator was highest in clone M2 and low in both clones H and L. Clone M2 exhibited the highest chemotactic activity toward diluted Matrigel, whereas clone L had the lowest activity. On the whole, these clones showed heterogenous interactions with an extracellular matrix. It is suggested that the attachment activity to basement membrane and the type IV collagenolytic activity of the cells may be positively correlated with their metastatic potential, whereas the production of urinary-type plasminogen activator was negatively correlated, but confirmation of these findings awaits further study.