Expression of Neural Cell Adhesion Molecule in Pancreatic Cancer

Abstract

Neural cell adhesion molecule (NCAM) has been found to be a significant factor for survival in various solid tumors. In the present study, we examined the expression of NCAM in exocrine tumors of the pancreas by immunohistochemistry, using two monoclonal antibodies against NCAM and polysialic acid (MAB735). Expression of NCAM was seen mainly in the cytoplasm of the following cells: regenerating duct cells among neoplastic tissue, hyperplastic islet cells, intrapancreatic nerves and ganglia, as well as tumor cells. There was no reactivity with MAB735. We found a significant correlation between intense NCAM expression (i.e., expression in more than 50% of all tumor cell mass) and survival rates in tubular adenocarcinoma, particularly moderately differentiated tumors (p < 0.05). There was no statistically significant relation between NCAM reactivity and tumor stage or any of the clinicopathologic parameters described by the Japan Pancreas Society (p > 0.05). We conclude that the expression of NCAM in tubular adenocarcinoma of the pancreas, particularly in moderately differentiated tumors, has a significant impact on the overall patient survival.

Blockade of natural killer cell‐mediated lysis by NCAM140 expressed on tumor cells

“…The therapeutic use of anti-NCAM antibodies will be limited, however, by the possibility that metastasis formation may be enhanced through NCAM blocking. NCAM expression tends to be lost in metastatic lesions [18][19][20]23 and, conversely, aberrant expression of L1-CAM in carcinomas was reported to enhance tumor growth and cell migration. According to the herein reported findings, both conditions would augment tumor cell recognition by NK cells.…”

“…13 NCAM expression is a marker for neuroendocrine carcinomas of the lung 14,15 and in other organs. 16,17 Aberrant expression has also been detected in renal cell carcinoma, 18 pancreatic adenocarcinoma and b cell tumors, 19,20 in tumors of the salivary gland 21 and gall bladder, 22 and cases of breast and colon carcinoma. 23,24 In line with the adhesive functions of NCAM, low or absent NCAM expression in carcinomas was correlated with a metastatic phenotype and poor survival rates.…”

“…23,24 In line with the adhesive functions of NCAM, low or absent NCAM expression in carcinomas was correlated with a metastatic phenotype and poor survival rates. [18][19][20]23 NCAM is constitutively expressed by NK and a small subset of T cells with MHC-unrestricted cytotoxicity. 25,26 The role of NCAM expressed by NK cells is controversial.…”

Valproic acid inhibits adhesion of vincristine- and cisplatin-resistant neuroblastoma tumour cells to endothelium

“…Diminished expression of NCAM was also associated with clinically aggressive colon cancers (Sampson-Johannes et al, 1996;Roesler et al, 1997;Huerta et al, 2001), and dissemination of pancreatic b-tumour cells (Perl et al, 1999;Cavallaro et al, 2001). Tezel et al (2001) suggested that NCAM expression in tubular adenocarcinoma of the pancreas has a significant impact on overall patient survival. We recently demonstrated an inverse correlation between NCAM expression and NB cell adhesion, assessed on 11 NB cell lines.…”

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

“…NCAM has been shown to play an important role in the progression to tumor malignancy. Both the shift of the adult NCAM 120-kDa isoform to the embryonic 140-and 180-kDa isoforms and a general downregulation of NCAM expression are associated with poor prognosis in a few cancer types [50,51]. In a transgenic mouse tumor model of pancreatic b cell carcinogenesis (Rip1Tag2), loss of NCAM leads to the formation of lymph node metastasis mediated by the increased expression of the lymphangiogenic factors VEGF-C and D and with it upregulated peri-tumoral lymphangiogenesis [52,53].…”