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Organ-specific pancreatic tumor growth properties and tumor immunity

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TLDR
The results show that the growth properties and immunological rejection of pancreatic tumors is affected by the organ site at which the tumor grows.
Abstract
We established a model of orthotopic injection of a syngeneic pancreatic tumor cell line in C57BL/6 mice and evaluated the effects of organ site on induction of immunity to a tumor-specific antigen, MUC1. Mice were challenged with a syngeneic pancreatic adenocarcinoma cell line that expressed MUC1 (Panc02-MUC1) by orthotopic injection into the pancreas, or by subcutaneous injection. Tumor cells injected into the pancreas grew much faster than those injected subcutaneously. Mice challenged subcutaneously with Panc02-MUC1 rejected tumors or developed slowly growing tumors that were negative for MUC1 expression. In contrast, mice challenged orthotopically into the pancreas developed progressive tumors that were positive for MUC1 expression. Sera from mice that rejected PancO2-MUC1 (tumor-immune mice) showed no detectable IgG1 and IgM titers against the MUC1 tandem-repeat peptide, whereas mice with progressive tumor growth had significant titers of IgG1 and IgM specific for MUC1. This suggests that the humoral immune response was ineffective in mediating tumor rejection. The results show that the growth properties and immunological rejection of pancreatic tumors is affected by the organ site at which the tumor grows.

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References
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Journal ArticleDOI

Specific, major histocompatibility complex-unrestricted recognition of tumor-associated mucins by human cytotoxic T cells

TL;DR: Detailed studies performed with one of the cytotoxic T-cell lines from pancreatic cancer patients show that it recognizes a specific antigen, a large and heavily glycosylated mucin molecule, expressed on pancreatic and breast tumors and tumor cell lines.
Journal ArticleDOI

Cloning and sequencing of a human pancreatic tumor mucin cDNA.

TL;DR: The cDNA and deduced amino acid sequence of the pancreatic mucin sequence was over 99% homologous with a mucin cDNA sequence derived from breast tumor mucin, even though the native forms of these molecules are quite distinct in size and degree of glycosylation.
Journal ArticleDOI

A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens

TL;DR: Immunohistochemical analysis of the antigenic phenotype of the transplanted human pancreatic tumors showed a similar pattern of expression of two different human tumor-associated antigens in the transplants tumors when compared with the original surgical biopsy, suggesting similarity between the two.
Journal Article

Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma recognize an epitope present on the protein core of a mucin molecule preferentially expressed by malignant cells.

TL;DR: The data suggest that the highly repetitive nature of the mucin allows cross-linking of the T-cell receptor on mucin-specific T-cells and therefore accounts for the lack of MHC restriction seen in the tumor-reactive CTLs of patients with breast adenocarcinoma.
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