Differential distribution of basement membrane type IV collagen α1(IV), α2(IV), α5(IV) and α6(IV) chains in colorectal epithelial tumors

Abstract

In this study, we examined the relationship between the histopathological grade and immunohistochemical localization of six genetically distinct type IV collagen alpha chains, the major component of basement membrane (BM), in normal and neoplastic colorectal tissues. In the normal colorectal mucosa, alpha1/alpha2(IV) and alpha5/alpha6(IV) chains were stained in all epithelial BM. However, alpha3/alpha4(IV) chains were restrictively immunostained in the BM of the apical surface epithelium. Similar immunostaining profiles for alpha1/alpha2(IV) and alpha5/alpha6(IV) chains were observed in tubular adenomas with mild/moderate atypia. However, in intramucosal carcinomas, both alpha1/alpha2(IV) chains were linearly stained in the BM of cancer cell nests, while the assembly of alpha5/alpha6(IV) chains into the BM was inhibited in a discontinuous or negatively stained pattern. The normal colorectal mucosa forms a second network of BM composed of alpha5/alpha6(IV), partly alpha3/alpha4(IV) chains, in addition to the classic network of alpha1/alpha2(IV) chains. The differential immunohistochemical localization of the type IV collagen alpha5/alpha6 chains could be one diagnostic marker for the invasiveness of colorectal cancer.

Loss of Expression of Type IV Collagen α5 and α6 Chains in Colorectal Cancer Associated with the Hypermethylation of Their Promoter Region

“…In all of the normal mucosa ( Figure 1, A-H), the ␣1(IV)/ ␣2(IV) chains and the ␣5(IV)/␣6(IV) chains were stained in a continuous linear pattern in the BM of the surface epithelium and crypts ( Figure 1, C-F; black arrows). As shown in the previous report, 13 the ␣3(IV)/ ␣4(IV) chains were expressed only in the BM of apical surface of epithelium (data not shown). The ␣1(IV)/ ␣2(IV) chains were also expressed in the BM of the capillary endothelium ( areas of the submucosa and the muscularis propria, no expression of the ␣5(IV)/␣6(IV) chains was seen around the cancer cell nests in all of the 12 cases.…”

“…However, the biological activity of the ␣6(IV) chain has not been fully researched. Because the specific loss of the ␣5(IV)/ ␣6(IV) chains reported to occur in many types of cancers, 8,10,12,13,31,32 the further research as to the biological role of the ␣6(IV) chain for cancer prevention is expected.…”

“…23 Immunohistochemical staining was performed on 4-m-thick serial sections from paraffin-embedded tissue blocks according to the previous protocol. 13 Briefly, for the immunostaining of the ␣1(IV) to ␣6(IV) chains, deparaffinized sections were pretreated for antigen retrieval by autoclave heating (132°C, 303 kPa) in 10 mmol/L citrate buffer (pH 3.3) for 5 minutes. These sections were blocked for endogenous peroxidase activity with 3% H 2 O 2 in methanol for 60 minutes and then washed in phosphate-buffered saline (PBS).…”

Dynamics of the basement membrane in invasive epithelial clusters inDrosophila

“…It is important to note that degradation of the ECM at the leading edge of migrating clusters is essential for tumour progression, and examples of cancer cells showing a reduction or absence of some basement membrane markers, including Collagen IV, have been reported. In particular, human α3/α4 type IV Collagen is found at the apical surface in normal colon tissue, but is absent in colorectal neoplastic cells (Hiki et al, 2002), making the differential distribution of type IV collagens potential diagnostic markers for the invasiveness of cancer cells. The BC model will be central for future studies aimed at understanding BM dynamics and function in invasive clusters.…”

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

“…In particular, altered collagen a5/a6 production and assembly were found to be associated with increased malignancy in this disease (Hiki et al, 2002;Ikeda et al, 2006). These studies demonstrate that the growth of CRC tumors at the primary site is associated with loss of collagen production.…”