Riminucci M, Corsi A, Peris K, Fisher L W, Chimenti S, Bianco P
Department of Experimental Medicine, Laboratory of Pathology, University of L'Aquila, Italy.
Calcif Tissue Int. 2003 Sep;73(3):281-9. doi: 10.1007/s00223-002-2134-y.
Bone sialoprotein (BSP) is a member of the SIBLINGS family, normally restricted to the skeleton, but it has been shown to be ectopically expressed in some human invasive carcinomas. BSP expression in human cancer was initially associated with the ability of BSP-expressing tumors to metastasize to bone, although the mechanism whereby BSP expression should facilitate homing of cancer cells to the bone marrow environment has remained unexplained. More recently, clinical and experimental data have converged in highlighting a potential link between BSP expression and tumor invasiveness in general. We show here that human malignant melanoma cells express BSP in vivo as a function of extent of local invasion, and that expression of BSP mRNA and protein in melanoma cells is associated with the expression of the transcriptional regulator of osteogenic cell differentiation, Cbfa1/Runx2. It has been well established that expression of Cbfa1/Runx2 in the mouse is normally restricted to bone-forming cells. In the mouse, Cbfa1/Runx2 dictates osteogenic differentiation of mesodermal cells by regulating bone-specific genes. Since it also regulates expression of at least two matrix metalloproteases implicated in tumor invasion and metastasis (collagenase 3, membrane type 1 matrix metalloproteinase), we propose that the relationship between BSP expression and an invasive behavior in human epithelial cancer cells may be rooted in a common transcriptional control exerted by Cbfa1.
骨唾液蛋白（BSP）是SIBLINGS家族的成员，通常仅在骨骼中表达，但已证实在某些人类浸润性癌中存在异位表达。BSP在人类癌症中的表达最初与表达BSP的肿瘤向骨转移的能力相关，尽管BSP表达促进癌细胞归巢至骨髓环境的机制仍不清楚。最近，临床和实验数据都集中表明BSP表达与肿瘤侵袭性之间可能存在潜在联系。我们在此表明，人类恶性黑色素瘤细胞在体内表达BSP是局部侵袭程度的函数，并且黑色素瘤细胞中BSP mRNA和蛋白的表达与成骨细胞分化的转录调节因子Cbfa1/Runx2的表达相关。众所周知，Cbfa1/Runx2在小鼠中的表达通常仅限于成骨细胞。在小鼠中，Cbfa1/Runx2通过调节骨特异性基因来决定中胚层细胞的成骨分化。由于它还调节至少两种与肿瘤侵袭和转移有关的基质金属蛋白酶（胶原酶3、膜型1基质金属蛋白酶）的表达，我们提出BSP表达与人类上皮癌细胞侵袭行为之间的关系可能源于Cbfa1施加的共同转录控制。
