Psammoma bodies (PBs), characterized as calco-spherules with concentric laminations, are common in serous
tumors of the ovary. However, there is no agreements as to how the PBs are formed. Bone morphogenetic protein-2 (BMP-2) has recently been proposed to be involved in the calcification of
tumor cells and recent electron microscopic studies demonstrated the presence of
type IV collagen in PBs. Based on this evidence, we postulated a possibe role for BMP-2 and
type IV collagen in the formation of PBs in
ovarian cancer. We examined the expression of BMP-2 and typle IV
collagen by immunohistochemistry and reverse transcription PCR (RT-PCR) in PBs-forming (NK-211) and -non-forming (SHIN-3, KF-1, A2780, KK-92, KOC-2S, SKOV-3, OMC-3, MN-1, EC, and KEN-3)
ovarian cancer cell lines in vitro and in surgical specimens of serous
adenocarcinoma (SA) with/without PBs and
mucinous adenocarcinoma (MA) of the ovary. Cellular growth of cell lines was also evaluated by their doubling time in vitro. Transcripts for BMP-2
mRNA were detected by RT-PCR in all cell lines. By immunohistochemistry, BMP-2
protein expression was positive in 45% (5 out of 11) of cell lines. 36.4% (4 out of 11) were positive for
type IV collagen. PBs-forming NK-211 was intensively positive for both BMP-2 and
type IV collagen. In addition, NK-211 demonstrated extremely slow growth with a doubling time of 450 hours. In surgical specimens, BMP-2 vs.
type IV collagen positivities in
tumor cells were 100% (20 out of 20) vs. 40% (8 out of 20) in SA with PBs, 61.1% (11 out of 18) vs. 0% (0 out of 18) in SA without PBs and 75% (9 out of 12) vs. 0% (0 out of 12) in MA. In PBs themselves, 100% (20 out of 20) positivity for BMP-2 and 80% (16 out of 20) for
type IV collagen was shown. These results raise the possibility that BMP-2 and
type IV collagen-producing slow growing
tumor cells form PBs in
ovarian cancer.