Stromal Cells Promote Bone Invasion by Suppressing Bone Formation in Ameloblastoma.

Gul San Ara Sathi, Ryo Tamamura, Silvia Susana Borkosky,

Hiroyuki Matsuda, Mehmet Gunduz, Mathieu Bernard Lefevre,

Mahmoud Al Sheikh Ali, Hitoshi Nagatsuka, Noriyuki Nagai

Department of Oral Pathology and Medicine,

Graduate School of Graduate School of Medicine,

Dentistry and Pharmaceutical Sciences, Okayama University

In ameloblastoma, interaction between the stroma and tumor cells and their subsequent roles in bone invasion has not yet been investigated. In the present study, we focused on the stromal variation and role of stroma-tumor cell interaction in impaired bone formation as well as enhanced bone resorption in ameloblastoma. 54 areas from 22 blocks were chosen based on the presence of bone tissue, stroma and tumor nests. Four types of stroma were observed histologically; fibrous, desmoplastic, myxoid and myxoid with hyalinization. Osteoblast and osteoclast were counted using H & E sections and immunohistochemistry with CD68. After histomorphometrical analysis, only fibrous and myxoid types of stroma were distinctly identified. sFRP-2, TGF-b1, and RANKL revealed a strong expression in myxoid type compared to the normal stroma. BMP-2 was negative in myxoid type whereas positive in normal stroma. Fibrous type stroma showed weak expression of all antibodies except RANKL compared to the myxoid. This finding suggests that bone destruction without proportional bone formation is more remarkable in myxoid type stroma. And the tumor cells only induce a favorable microenvironment for tumor invasion by secreting sFRP-2, RANKL and IL-6. In ameloblastoma, stroma acts both in bone resorption and suppression.