Cell adhesion molecules (CAM) have been implicated in the process of cancer metastasis. However, the interactions of metastatic tumor cells with organ parenchymal cells-hepatocytes particularly the relevance of tumor-cell-hepatocyte adhesion to liver metastasis is still not fully understood. We have investigated the role of tumor cell-hepatocyte interaction in liver metastasis using liver metastatic subline H-59 of the Lewis lung carcinoma. A monoclonal antibody (MAb) C-11 was produced which was highly specific to liver metastatic H-59 cells. Our in vitro studies showed that this MAb and its F(ab)2 fragments could block tumor H-59 cell adhesion to hepatocytes. The molecule detected by MAb C-11 on H-59 cells as well as on hepatocytes was a 64-71 kDa plasma membrane glycoprotein (designated C-11 BP). We found that this molecule contains approximately 43% of N-linked carbohydrates which were not involved in MAb C-11 recognition, but participated in the adhesion process. MAb C-11 could also block the stimulatory effect of hepatocytes on tumor cell proliferation indicating that the adhesion of H-59 cells to hepatocytes may be necessary for tumor cell growth. The in vivo role of the C-11 BP was subsequently tested and it was shown that MAb C-11 and its F(ab)2 fragments could significantly reduce the number of hepatic metastases when used to pretreat H-59 cells before intrasplenic injection, or when inoculated directly into the animals by the intraperitoneal and intravenous routes. This inhibitory effect resulted in an increase in the survival time of tumor-inoculated mice. In additional studies, a second molecule namely the membrane-associated endoplasmic reticulum protein ERp-72 was also implicated in the adhesion of H-59 cells to the hepatocytes, however its role in vivo remains to be confirmed. Our results suggest that CAM involved in tumor-hepatocyte adhesion play an important role in liver metastasis. Monoclonal antibody against tumor cell surface adhesion molecul
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.40275 |
| Date | January 1995 |
| Creators | Wang, Jian, 1961- |
| Contributors | Brodt, Pnina (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Surgical Research.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001496038, proquestno: NN12506, Theses scanned by UMI/ProQuest. |
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