The Stem Cell Factor–c-kit System and Mast Cells in Human Pancreatic Cancer

Abstract

SUMMARY:Stem cell factor (SCF) and its receptor c-kit take part in the regulation of developmental processes of mast cells, hematopoietic stem cells, and melanocytes, as well as in the growth control of human malignancies. To explore the possible role of the SCF-c-kit system and of mast cells in pancreatic cancer, the concomitant expression and distribution of the two molecules were examined in 17 normal and 26 cancerous human pancreatic tissues and in 6 cultured pancreatic cancer cell lines. Mast cell distribution was also evaluated in the same tissue samples. In addition, the effects of SCF and of the c-kit tyrosine-kinase inhibitor STI571 on the growth of the cancer cell lines and of the normal pancreatic ductal cell line TAKA-1 were assessed. SCF immunoreactivity was absent in acinar, ductal, and islet cells of the normal pancreas and faint in pancreatic cancer tissues and cell lines. In contrast, c-kit was clearly present in some normal and hyperplastic ducts of the normal pancreas, in the cancer cells of 73% of the tumor samples, and in all the cell lines tested. Mast cells, identified by tryptase and chymase immunostaining on consecutive tissue sections, showed immunoreactivity for SCF and c-kit in both normal and cancerous specimens and their number was significantly increased (p ϭ 0.03) in pancreatic cancer compared with the normal pancreas. SCF showed a dose-dependent growth inhibitory effect on TAKA-1 cells (p Ͻ 0.001), whereas pancreatic cancer cells were resistant to the SCF-induced growth inhibition. Nonetheless, the growth of TAKA-1 cells and pancreatic cancer cells was inhibited by the c-kit tyrosine kinase inhibitor STI571. In conclusion, the SCF-c-kit system, possibly with the contribution of mast cells, may have a growth-regulating role in the normal pancreas, which is altered during malignant transformation. (Lab Invest 2002, 82:1481-1492.

Cellular hamartoma resembling gastrointestinal stromal tumor: a solid tumor of the pancreas expressing c-kit (CD117)

“…Experimental studies 27 localized the c-kit protein to ducts of the fetal rat pancreas and to normal and hyperplastic ducts of the normal pancreas. 28 Welsh et al 29 postulated that tyrosine kinases may play a role in beta-cell replication, differentiation (neoformation) and survival, as ducts are thought to harbor beta-cell precursor cells. The CD34 and CD117-positive stroma cells in our two cases seem to be matrixproducing cells.…”

Expression of the proto-oncogene c-KIT in normal and tumor tissues from colorectal carcinoma patients

“…Several studies have suggested the importance of c-KIT expression in a wide variety of human malignancies besides CML and GISTs, including germ cell tumors, smallcell lung carcinoma (SCLC), neuroblastoma, melanoma, ovarian carcinoma, breast carcinoma (reviewed in [4]) and, more recently, both exocrine [17] and endocrine [18] pancreatic tumors. However, in most of these cases the role of c-KIT in the neoplasia is not completely understood.…”

A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase

“…Pancreatic cancer is amongst the most lethal and least common human cancers and has been linked to diabetes and chronic pancreatitis [66]. High levels of c-Kit expression are also found on pancreatic neoplastic cells and throughout the duct of the cancerous pancreas [67], indicating that SCF-c-Kit interactions have profound implications for pancreatic cancer cell proliferation and invasiveness. While cancer aetiology is varied, both somatic and germline mutations in the SCF allele have been linked to testicular cancer.…”