HEPACAM1 and 2 are differentially regulated in canine mammary adenomas and carcinomas and its lymph node metastases

Abstract

BackgroundCell adhesion is an important regulator of cell growth and motility. Recently the hepatocyte cell adhesion molecules 1 and 2 (HEPACAM1 and 2), members of the immunoglobulin family of adhesion genes, have been identified. HEPACAM1 is involved in negative cell cycle regulation via p53, p21 and p27 signalling but also mediates increased human breast cancer cell spread. The role and expression pattern of HEPACAM2 has not been analyzed so far. In the present study we quantified gene expression levels of HEPACAM1 and 2 to evaluate their possible role during the carcinogenesis of canine mammary tumours.ResultsAdenomas displayed increased HEPACAM1 and 2 mRNA expression levels and decreased HEPACAM1 protein expression levels when compared to normal gland, carcinomas and lymph node metastases. In contrast, metastatic carcinomas, intravascular tumour cells and lymph node metastases had HEPACAM 1 protein and mRNA expression levels similar to normal gland but decreased HEPACAM2 mRNA expression when compared to normal gland of the same dog.ConclusionsHEPACAM1 and 2 seem to be important for cell-cell adhesion of normal and neoplastic canine mammary cells. The loss of HEPACAM1 protein expression in adenomas but not in carcinomas questions its role as a tumour suppressor at late stages of malignant transformation and indicates that it might rather be involved in physiologic mammary cell adhesion and canine mammary tumour metastasis. Furthermore, it can be speculated, whether HEPACAM2 plays a different role in malignancy and metastasis of canine mammary tumours since its transcriptional levels are different in carcinomas and their lymph node metastases when compared to HEPACAM1.

Structural determinants of interaction, trafficking and function in the ClC‐2/MLC1 subunit GlialCAM involved in leukodystrophy

“…) and the closest human homologue of GlialCAM, HepaCAM2 (Klopfleisch et al . ), which, similar to other IgCAM molecules, is also an oligomeric protein (Freigang et al . ; Soroka et al .…”

Exploration of the Correlations Between Interferon-γ in Patient Serum and HEPACAM in Bladder Transitional Cell Carcinoma, and the Interferon-γ Mechanism Inhibiting BIU-87 Proliferation

“…7 Surprisingly HEPACAM was hardly expressed in cancer samples, in contrast to the study by Klopfleisch et al, in which HEPACAM1 was expressed at the membrane in almost all canine breast carcinoma samples. 9 The entirely different phenomena might be the result of species variation.…”

“…7,8 Since existing studies were done at the gene level, HEPACAM protein expression in human tissue is unknown except for the report by Klopfleisch et al of HEPACAM expression in canine mammary adenoma and carcinoma, and lymph node metastasis. 9 However, in that study HEPACAM protein expression was up-regulated in canine mammary carcinoma and lymph node metastasis. This inconsistent HEPACAM phenomenon between the gene and protein levels led us to explore it in human bladder carcinoma.…”

The C-Type Lectin Receptor DCIR Is Crucial for the Development of Experimental Cerebral Malaria

“…CD3, CD31, and GrB immunostaining on paraffin or Davidson's sections was performed using the Avidin-Biotin Complex method as previously described (38). Primary Abs were diluted in TBS (50 mM, pH 7.6).…”