Expression of ADAM28 and IGFBP-3 Genes in Patients with Colorectal Cancer — A Preliminary Report

Abstract

Adamalisynes (ADAMs) play an important role in inter-membrane interactions, cell adhesion and fusion processes and protein shedding from the cell surface. Many reports indicate that members of the ADAMs family are overexpressed in human cancer. The aim of the present study was to evaluate ADAM28 and Insulin Like Growth Factor Binding Protein-3 (IGFBP-3)) gene expression in colorectal carcinoma tissues with regard to the overweight or obese status of the patients using an oligonucleotide micro array technique. Fresh tissue specimens were obtained from colorectal cancer patients during surgical treatment. Eighteen specimens from tumour and 18 normal tissue specimens from colorectal cancer patients at clinical stages III and IV were analysed. The examined patients were divided into two groups; those with BMI;::25 and those with normal BMI. The control group consisted of 18 specimens of non-neoplastic colon tissues, which were divided between overweight/obese and normal body weight patients. The gene transcriptional activity from the specimens was analysed using an oligonucleotide microarray technique. Microarrays and rinsing and marking solutions were prepared according to the procedure in the Gene Expression Analysis Technical Manual. The following conclusions were made: i) change of ADAM28 and IGFBP-3 genes expression are present in the normal tissue in overweight/obese patients with colorectal cancer only; ii) the observed molecular variability of ADAM28 and IGFBP-3 expression may be an initial process of cancer proliferation; iii) the histopathologically normal surgical margin in this group of patients was not equal to the molecular margin.Adamalisynes (ADAM -a disintegrin and metalloproteinase domain), also known as MCDs (metalloprotease/disintegrin/cysteine rich protein), belong to a large family of zinc-dependent proteins referred to as methizines. Admalisynes is a group consisting of more than 30 type I transmembrane

MicroRNA-552 enhances metastatic capacity of colorectal cancer cells by targeting a disintegrin and metalloprotease 28

“…In consistent with findings in other cancer types, the change of ADAM28 and IGFBP-3 genes expression was only observed in normal tissues but not tumor tissues of overweight/obese patients with CRC, implying that alterations of the expression of ADAM28 and IGFBP-3 may be an initial process of cancer proliferation, despite the histopathologically normal surgical margin in this group of patients was not equal to the molecular margin [23]. In normal tissues, ADAM28 may play a protective role in cell survival.…”

“…The ADAM28 was screened as a potential target of miR-552 for further investigation, partially owing to a conserved seed sequence of this miRNA was possessed within the 3′UTR of its mRNA, and its crucial role in pathogenesis of many types of cancers, including the CRC, in which ADAM28 expression was correlated with a poor prognosis [22, 23, 37, 38], despite its role in CRC remained unclear [23]. To further explore the clinical relevance of ADAM28 with the clinic pathogenesis in human CRC, its expression was first evaluated in CRC tumor tissues and the matched adjacent non-tumor tissues by IHC staining against anti-ADAM28 antibody.…”

“…In the CRC, up-regulation of ADAM28 and IGFBP-3 genes in was only detected in the normal tissue of overweight/obese patients with CRC as determined by a qRT-PCR assay, but the histopathologically normal surgical margin in specimens was not equal to the molecular margin [23]. However, a controversial result was reported by Abe et al, by whom a co-expression of ADAM28 and phosphorylated v-src was found in neoplastic cells of the breast, lung, and colon carcinomas and some adenomas of the colon, but not in nonneoplastic colon mucosa, as determined by an IHC analysis [37].…”

“…For instance, ADAM28 was the most frequent and selective ADAM species expressing in the breast and lung carcinoma tissues, and the abundance of its transcripts was directly correlated with the capacity of cell proliferation and metastasis [19, 20]. Mechanistically, the oncogenic role of ADAM28-mediated cancer cell metastasis may be related with its ability to cleave factors including von Willebrand's factor (vWF) [15], insulin-like growth factor binding protein-3 (IGFBP-3) [23], and connective tissue growth factor (CTGF) [24], and to promote PSGL-1/P-selectin-mediated cell adhesion [25]. …”

“…In the CRC, the correlation of ADAM28 and CRC tumorigenesis has not yet been established, although transcripts of ADAM28 and IGFBP-3 genes in fresh CRC tumor specimens were primary examined in CRC patients with overweight or obese using a microarray analysis [23]. In consistent with findings in other cancer types, the change of ADAM28 and IGFBP-3 genes expression was only observed in normal tissues but not tumor tissues of overweight/obese patients with CRC, implying that alterations of the expression of ADAM28 and IGFBP-3 may be an initial process of cancer proliferation, despite the histopathologically normal surgical margin in this group of patients was not equal to the molecular margin [23].…”