Hamilton D, Mallinger R, Millesi H, Engel A, Baumgartner G, Raderer M
Department of Surgery, University School of Medicine, University of Vienna, Austria.
Anticancer Res. 2001 Nov-Dec;21(6A):3909-13.
Prostate cancer metastases induce a predominantly osteoblastic response in bone tissue, resulting in new bone formation and associated morbidity; however, the mechanisms of these tumor-host responses are not fully understood.
Supernatants of prostate (PC3, DU145, LNCaP), breast (BT20, ZR-75-1), colon (SW620, Colo 320DM), pancreatic (ASPC1, Capan-1), renal cell (ACHN) and hepatoma (HepG2) cell lines were tested for their capacity to modulate proliferation, activity of alkaline phosphatase (ALP) and CD99/MIC2 expression in AHTO-7 (large T antigen transfected human trabecular osteoblasts) cells in vitro.
Osteoblastic stimulation is not restricted to prostate cancer derived conditioned media CM and high activity is found in CM from Capan-1, HepG2 and ACHN lines. Furthermore these CM down-regulate the expression of the CD99/MIC2 antigen in comparison to medium by AHTO-7 cells as detected by HBA-71 immunofluorescence, with the exception of prostate cancer-derived CM. Induction of the differentiation marker ALP was detected in response to CM derived from Capan-1, BT-20 and Colo320DM. Stimulation of the proliferation of AHTO-7 cells (105-138% of control), induction of ALP (1.17-5.29-fold) and down-regulation of CD99 (13.6-57.5%) exhibited no correlation. CM derived from PC3 and LNCaP metastatic prostate cancer cell lines specifically resulted in the retention/stimulation of the expression of CD99/MIC2 in AHTO-7 cells in contrast to all other cell lines tested.
The CD99/MIC2 antigen, which is expressed on human osteoblasts and osteosarcoma cells, seems to constitute a new and independent response marker of osteoblasts in the triggering of osteoblastic reaction by prostate cancer cells.
前列腺癌转移在骨组织中主要引发成骨反应,导致新骨形成及相关发病情况;然而,这些肿瘤与宿主反应的机制尚未完全明确。
检测前列腺(PC3、DU145、LNCaP)、乳腺(BT20、ZR-75-1)、结肠(SW620、Colo 320DM)、胰腺(ASPC1、Capan-1)、肾细胞(ACHN)和肝癌(HepG2)细胞系的上清液在体外调节AHTO-7(大T抗原转染的人小梁成骨细胞)细胞增殖、碱性磷酸酶(ALP)活性及CD99/MIC2表达的能力。
成骨刺激并不局限于前列腺癌来源的条件培养基CM,在Capan-1、HepG2和ACHN细胞系的CM中发现高活性。此外,通过HBA-71免疫荧光检测发现,与AHTO-7细胞的培养基相比,这些CM下调了CD99/MIC2抗原的表达,但前列腺癌来源的CM除外。在对Capan-1、BT-20和Colo320DM来源的CM反应中检测到分化标志物ALP的诱导。AHTO-7细胞增殖的刺激(对照的105 - 138%)、ALP的诱导(1.17 - 5.29倍)和CD99的下调(13.6 - 57.5%)之间无相关性。与所有其他测试细胞系相比,源自PC3和LNCaP转移性前列腺癌细胞系的CM特异性导致AHTO-7细胞中CD99/MIC2表达的保留/刺激。
在人成骨细胞和骨肉瘤细胞上表达的CD99/MIC2抗原似乎构成了前列腺癌细胞触发成骨反应时成骨细胞新的独立反应标志物。