Cartilage-Specific Matrix Protein Chondromodulin-I Is Associated with Chondroid Formation in Salivary Pleomorphic Adenomas

Abstract

Chondromodulin-I (ChM-I) is a novel cartilage-specific matrix protein. In the growth plates of the long bones, ChM-I was shown to be expressed in mature to upper hypertrophic chondrocytes, and to be deposited in the cartilage matrix. As ChM-I strongly inhibits angiogenesis, cartilage is avascular. Also, ChM-I has bifunctional activity against chondrocyte proliferation. On the other hand, pleomorphic adenomas of the salivary glands frequently have chondroid elements. To elucidate the relationship between chondroid formation and hypovascularity in salivary pleomorphic adenomas, we immunohistochemically examined the expression and localization of ChM-I in 35 cases of this tumor. ChM-I was immunolocalized to the lacunae in the chondroid elements of pleomorphic adenomas (100%). Type II collagen and aggrecan were immunolocalized throughout the matrix around lacuna cells of the chondroid element (100%, 91.7%), and ChM-I was infrequently immunolocalized to the spindle-shaped myoepithelial cells in the myxoid element (37.5%). Fibroblast growth factor-2 was strongly immunolocalized to the lacuna cells in the chondroid element (100%), among the neoplastic myoepithelial cells in the myxoid elements (96.9%), and on the basement membranes around the solid nests of neoplastic myoepithelial cells (71.4%). Although CD34 is a marker of endothelial cells, CD34 was expressed in the endothelial cells in only a few areas around the epithelial elements and in the fibrous element of pleomorphic adenomas. No signals for CD34 were observed in chondroid elements in pleomorphic adenomas (P < 0.001), but a few signals were seen in the myxoid elements (P < 0.05). These findings suggested that lacuna cells and neoplastic myoepithelial cells expressed ChM-I, and that this molecule may play an important role in hypovascularity and chondroid differentiation in pleomorphic adenoma. In conclusion, pleomorphic adenoma expressed ChM-I, which is involved in hypovascularity and chondroid formation in this type of tumor.

Cartilaginous features in matrix-producing carcinoma of the breast: four cases report with histochemical and immunohistochemical analysis of matrix molecules

“…Aggrecan deposition was also seen in myxoid and chondroid stroma of salivary pleomorphic adenomas, whereas type II collagen deposition was observed in only chondroid stroma of pleomorphic adenomas. 5,6,22 Histochemically, toluidine blue stain also showed marked metachromasia of the stroma. The matrix nature of matrix-producing carcinoma of the breast was similar to that of salivary pleomorphic adenomas and normal cartilage.…”

“…3 This macromolecule deposits in the hypertrophic zones of growth plate cartilage, 4 although it was reported to deposit in the salivary pleomorphic adenoma, which frequently showed mesenchyme-like elements, including myxoid and chondroid tissues. 5,6 Type II collagen, which is a cartilage-specific major collagen, and chondromodulin-I (ChM-I), which is cartilage-specific noncollagenous matrix protein, 4,7,8 are deposited in the normal cartilaginous matrix. These molecules can be useful markers of cartilaginous differentiation.…”

A Green Tea Component Suppresses Posttranslational Expression of Basic Fibroblast Growth Factor in Colorectal Cancer

“…Factor VIII is a marker for endothelial cells used to evaluate angiogenesis, 21 and bFGF is a proangiogenic factor in adenomas as well as adenocarcinomas. 22 Immunostaining for Factor VIII on control and EGCG-treated small intestinal tumors suggested that endothelial-lined capillaries were more prevalent in the control group, compared with EGCG-treated tumors ( Figure 5D, bottom). Finally, ELISA assay was performed using the small intestinal tissue samples from the respective 3 groups, and results showed significant suppression of bFGF by EGCG (P < .05) compared with controls using the Dunnett test ( Figure 5E).…”

Expression and localization of cartilage-specific matrix protein chondromodulin-I mRNA in salivary pleomorphic adenomas

“…As binding between fibroblast growth factor (FGF) and FGF receptor-1 was reported to inhibit terminal differentiation of chondrocytes and calcification in vitro [12], we have reported that co-expression of FGF-2 and FGF receptor-1 in lacuna cells may play an essential role in the inhibition of ossification of the chondroid element in pleomorphic adenomas [14]. Although FGF-2 is also known to be a strong angiogenic factor [2,5,20], pleomorphic adenoma is a hypovascular tumor, due to the low density of CD34-positive endothelial cells [16]. Cartilage-specific matrix protein, bovine chondromodulin-I (ChM-I), has been shown to be a strong inhibitory factor against angiogenesis in vitro [8,9], and human ChM-I has also been cloned [10].…”

“…Cartilage-specific matrix protein, bovine chondromodulin-I (ChM-I), has been shown to be a strong inhibitory factor against angiogenesis in vitro [8,9], and human ChM-I has also been cloned [10]. Recently, using an immunohistochemical technique, we have shown that ChM-I is deposited in the inter-territorial matrix of the chondroid element of pleomorphic adenoma [16]. As ChM-I serves as a barrier against the angiogenic property of FGF-2, pleomorphic adenomas are hypovascular tumors.…”