Type IV collagen, the major component of basement membrane (BM), demonstrates a stage- and position-specific distribution of its isoforms during tooth development. To determine its localization in BM of benign odontogenic neoplasms, immunohistochemistry using six anti-alpha(IV) chain-specific monoclonal antibodies was performed. Results disclosed that BM demonstrated an irregular alpha(IV) chain profile in tooth germ as compared to benign odontogenic neoplasms. No alpha3(IV) chains were detected. Expression of alpha1(IV)/alpha2(IV) and alpha5(IV)/alpha6(IV) chains was stronger in desmoplastic than in ordinary ameloblastomas. The adenomatoid odontogenic tumor distinctly expressed these chains in BM of cribriform areas and hyaline materials (which was also alpha4(IV)-positive), but weakly around epithelial whorls/rosettes/nests and mineralized foci. These five chains also stained BM and tumor cells of ameloblastic fibroma and odontoma but not the inductive hard tissues. The present results suggest that modification and remodeling of BM collagen IV alpha chains occur during odontogenic neoplasms progression.

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Type IV collagen, the major component of basement membrane (BM), demonstrates a stage- and position-specific distribution of its isoforms during tooth development. To determine its localization in BM of malignant odontogenic neoplasms, immunohistochemistry using six anti-alpha(IV) chain-specific monoclonal antibodies was performed. Results disclosed that BM demonstrated an irregular alpha(IV) chain profile in tooth germ as compared to benign odontogenic neoplasms. No alpha3(IV) chains were detected. Expression of alpha1(IV)/alpha2(IV) and alpha4(IV), alpha5(IV)/alpha6(IV) chains was ameloblastic fibro-odontosarcoma, but not the inductive hard tissues. Ameloblastic carcinoma showed specific alpha1(IV)/alpha2(IV) chain loss, while primary intraosseous carcinoma demonstrated a discontinuous alpha1(IV)/alpha2(IV) and alpha5(IV)/alpha6(IV) staining pattern. The present results suggest that modification and remodeling of BM collagen IV alpha chains occur during malignant odontogenic neoplasms' progression.

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Destruction of basement membrane is an important element in invasion of cancer cells. Type IV collagen, the major component of basement membrane, has six distinct α chains. Matrix metalloproteinases (MMPs) are enzymes that resolve extracellular matrix. Oral squamous cell carcinoma occurs through precancerous lesion epithelial dysplasia and carcinoma in situ. We investigated localization of six α chains and MMPs in normal oral mucosal tissue, precancerous lesions, early squamous cell carcinoma immunohistochemically. In normal oral mucosal tissue and epithelial dysplasia, α1 (IV), α2 (IV), α5 (IV) and α6 (IV) chains were detected continuously along basement membrane. In carcinoma in situ and early squamous cell carcinoma, either α5 (IV) and α6 (IV) chains or all α chains were not stained. In contrast, MMP-2 and MMP-9 that are members of type IV collagenase were stained at the parts of disappearance of α chains. This study suggested that the disappearance of α chains is an important element in carcinogenesis of oral squamous cell carcinoma.

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Destruction of basement membrane is an important element in invasion of cancer cells. Type IV collagen, the major component of basement membrane has six distinct α chains. Matrix metalloproteinases(MMPs) are enzymes that can resolve extracellular matrix. In this study, we investigated the localization of six α chains and MMPs in oral squamous cell carcinoma immunohistochemically. In well differentiated squamous cell carcinoma, the localization of α chains showed various patterns. α1 (IV), α2 (IV), α5 (IV) and α6 (IV) chains were stained in almost all basement membranes in the central of cancer. Unique staining with only α5 (IV) and α6 (IV) chains was also observed. In the invasive point of cancer, all α chains mainly became negative, but MMP-2 and MMP-9 were stained strongly. In poorly differentiated squamous cell carcinoma, both α chains and MMPs were not stained. Furthermore, we examined the correlation between distribution of α1 chain and invasive pattern of cancer. We found that the disappearence of α chains correlated closely with invasive activity of cancer.

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For the purpose of developing a hybrid type dentin with periodontal membrane implant, we conducted in vitro and in vivo experiments using a mouse dental papilla-derived cell line MDPC-23 to study anatomical and functional differentiation. Our results show that MDPC-23 cells possess dentin-inducing characteristics and differentiate into odontoblast-like cells extending cytoplasmic projection unilaterally.

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