Establishment and Characterization of Human Pancreatic Cancer Cell Lines in Tissue Culture and in Nude Mice

Abstract

Three human pancreatic cancer cell lines, designated as KP·IN, KP·2 and Kp·3 have been established in both tissue cultures and in nude mice. The Kp·IN and Kp·3 tumors were obtained from liver metastases of pancreatic tumors and the KP·2 tumor was of primary pancreatic origin. The patients' tumors from which KP·IN and Kp·2 were derived showed characteristics of adenocarcinoma, and the KP·3 tumor had adenosquamous carcinoma characteristics. Inoculations of samples from surgical specimens into athymic nude mice resulted in tumor formation, with the tumors histologically closely resembling the original neoplasms. Subcutaneous injections of the established cell lines also induced tumor formation and the tumors histologically resembled the original lesion in the cases of KP·2 and KP·3 tumors, but the KP·IN tumors in the mice were histologically different from the surgical specimen. The KP·IN, Kp·2 and Kp·3 cell lines have been cultured continuously in a medium Supplemented with 10% fetal calf serum for more than 20, 21 and 17 months, respectively. The Kp· 2 and KP·3 cell lines produced and released carbohydrate antigen 19·9 into the spent medium but the KP·IN cell line did not. KP·IN and KP·3, produced liver metastases after intrasplenic injection into nUde mice, whereas Kp·2 produced few liver colonies. Cell lines highly metastatic to the liver, Kp· INLs and KP·3Ls, were isolated from the liver colonies of KP·IN and KP·3, respectively. Carcinomas of the pancreas are one of the most frequent causes of cancer deaths in Japan, and the incidence is increasing. I) Biological models are necessary for the study of pancreatic cancer, in that little is known about the biology, chemotherapy, or metastasis of this neo· plasm. Thus, permanent cell lines and xenografts of human pancreatic cancers could provide information on the biological properties and therapeutic response of this tumor that could lead to effective approaches for treatment of this disease.to demonstrate metastatic activity in the liver from colon tumors has been carried out using intrasplenic (LS.)6 injections of cells. 15, 16) It is necessary to study an experimental model system to determine whether pancreatic tumor cells metastasize to the liver.

Expression of the Clustered NeuAcα2–3Galβ O-Glycan Determines the Cell Differentiation State of the Cells

“…Mucin-like protein DMBT1 binds to a variety of host proteins including IgA, C1q, lactoferrin, mucin 5B, and trefoil factor 2, which are all involved in innate immunity (34). The highly metastatic KP-3L cells were isolated from the liver colonies of pancreatic cancer KP-3 cells after injection into nude mice (35). The present results showed that MAb7 antigen was almost expressed in cytoplasm of some KP-3 cells, whereas all KP-3L cells expressed its antigen on the plasma membrane and in the conditioned medium.…”

Production of endothelin-1 and thrombomodulin by human pancreatic cancer cells

“…In this study, eight of the 12 cell lines were found to produce CA19-9, and several produced CEA or DUPAN-2 as well. The four remaining cell lines were characterised mainly by morphological analysis (Lieber et al, 1975;Yunis et al, 1977;Owens et al, 1979;Yamada et al, 1986;Ikeda et al, 1990), which suggested that they originated from pancreatic cancer.…”

“…FA-6 was a gift from N. Nagata (National Defense Medical College, Saitama, Japan) (Nagata et al, 1989). KP1N, KP2, KP3, H48N were established by A. Kono and colleagues (National Kyushu Cancer Center, Fukuoka, Japan) (Ikeda et al, 1990).…”

Microencapsulated tumor assay: Evaluation of the nude mouse model of pancreatic cancer

“…Although subcutaneous xenografts generally grow well and may be phenotypically malignant locally, they tend to form pseudocapsules, resembling encapsulated benign tumors rather than infiltrative malignancies, even when derived from undifferentiated or poorly differentiated aggressive cell lines. Importantly, subcutaneously injected human cancer cells only rarely metastasize to the parenchymatous organs and do not display the signs and symptoms that may arise as a consequence of tumor growth within visceral organs [9][10][11][12][13][14] . Thus, the subcutaneous model is of limited clinical value.…”

“…Tumor volume was calculated according with the formula V = length × width × depth/2 [9] . The growth curves were constructed accordingly.…”