Bone morphogenetic protein-2 and type IV collagen expression in psammoma body forming ovarian cancer

Psammoma bodies (PBs), characterized as calcospherules with concentric lami nations, are common in serous tumors of the ovary. However, there is no agr eements 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 cel ls and recent electron microscopic studies demonstrated the presence of typ e 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. W e examined the expression of BMP-2 and typle IV collagen by immunohistochem istry and reverse transcription PCR (RT-PCR) in PBS forming (NK-211) and -n on-forming (SHIN-3, KF-1, A2780, KK-92, KOC-2S, SKOV-3; OMC-3, MN-1, EC, an d KEN-3) ovarian cancer cell lines in vitro and in surgical specimens of se rous adenocarcinoma (SA) with/without PBs and mucinous adenocarcinoma (MA) of the ovary. Cellular growth of cell lines was also evaluated by their dou bling time in vitro. Transcripts for BMP-2 mRNA were detected by RT-PCR in all cell lines. By immunohistochemistry, BMP-2 protein expression was posit ive in 45% (5 out of 11) of cell lines. 36.4% (4 out of 11) were positive f or type IV collagen. PBS forming NK 211 was intensively positive for both B MP-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. 4 0% (8 out of 20) in SA with PBs, 61.1%(11 out of 18) vs. 0% (0 out of 18) i n SA without PBs and 75% (9 out of 12) vs. 0% (0 out of 12) in MA. In PBs t hemselves, 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 BM P-2 and type lV collagen producing slow growing tumor cells form PBs in ova rian cancer.