Differential Expression of Decorin by Human Malignant and Benign Vascular Tumors

Abstract

An increasing amount of evidence indicates that a small extracellular chondroitin/dermatan sulfate proteoglycan, decorin, is indirectly involved in angiogenesis. Given that angiogenesis is a sine qua non for tumor growth and progression, we attempted to examine whether human malignant vascular tumors differ from human benign vascular tumors in terms of their decorin expression and synthesis. CD31 immunostaining demonstrated that the human malignant vascular tumors Kaposi's sarcoma and angiosarcoma were filled with capillary-like structures, whereas in benign cavernous and capillary hemangiomas, blood vessels were not as abundantly present. By utilizing in situ hybridization and immunocytochemical assays for decorin, we showed that there was no detectable decorin mRNA expression or immunoreactivity within the tumor mass in the Kaposi's sarcoma or angiosarcoma group. Instead, decorin was expressed in the connective tissue stroma lining the sarcoma tissue. In contrast to sarcomas, in hemangiomas, decorin mRNA expression and immunoreactivity were observed also within the tumor mass, particularly in the connective tissue stroma surrounding the clusters of intratumoral blood vessels. Finally, distribution of type I collagen was found to be similar to that of decorin in these tumor tissues. Our findings can be explained with different states of angiogenesis in dissimilar growths. In sarcomas, angiogenesis is extremely powerful, whereas in hemangiomas, angiogenesis has ceased. Thus, decorin is likely to possess a suppressive effect on human tumor angiogenesis in vivo, as previously described by studies using different experimental models. Decorin certainly provides a usable biomarker for distinguishing between benign and malignant vascular tumors in patients.

Spindle Cell Hemangioma and Decorin Expression

“…The results demonstrated that immunoreactivity of decorin was clearly detectable in the connective tissue stroma within tumor nests. This finding is compatible with the previous study that demonstrated negative and positive expressions in Kaposi's sarcoma and benign hemangioma, respectively [4]. Localization of decorin staining is supposed to be similar to collagen I.…”

“…In addition, decorin has been shown to regulate endothelial cell-matrix interactions during angiogenesis [5]. Furthermore, a current publication on benign and malignant vascular tumors demonstrated that expression patterns of decorin were differed from malignant to benign vascular tumors [4]. They showed that there was no detectable decorin immunoreactivity within the tumor mass in the Kaposi's sarcoma or angiosarcoma group.…”

“…In contrast to sarcomas, in benign hemangiomas, decorin immunoreactivity were observed also within the tumor mass, particularly in the connective tissue stroma surrounding the clusters of intratumoral blood vessels. They suggested that decorin might possess a suppressive effect on tumor angiogenesis and provide a useful biomarker to differentiate benign and malignant vascular tumors in patients [4].…”

“…However, several studies have revealed that the lesion is not a neoplasm possessing metastatic potential, but a reactive cellular proliferation [2]. Recently, the proteoglycan decorin was demonstrated to play a key role in angiogenesis in normal and tumor-associated endothelium [3][4][5]. In this study, we measured decorin expression immnohistochemically in 2 SCH cases and examine feasibility of decorin stating for distinguishing between SCH and malignant vascular tumors.…”

Decorin Antagonizes the Angiogenic Network

“…This is further substantiated by a recent report where the expression of decorin was evaluated as a function of tumor malignancy. Sarcomas exhibited almost a complete absence of decorin in contrast to hemangiomas, where decorin was predominantly detected in the surrounding stroma (74). Aside from the potent pro-migratory, pro-invasive, and pro-survival roles inherent with aberrant Met activation (75), the Met signaling axis is powerfully pro-angiogenic, specifically promoting VEGFA-mediated angiogenesis (76,77).…”