Sharp Julie A, Waltham Mark, Williams Elizabeth D, Henderson Michael A, Thompson Erik W
University of Melbourne, Department of Surgery, St. Vincent's Hospital, Fitzroy, Australia.
Clin Exp Metastasis. 2004;21(1):19-29. doi: 10.1023/b:clin.0000017167.17065.61.
We have investigated the role of bone sialoprotein (BSP), a secreted glycoprotein normally found in bone, in breast cancer progression. To explore functions for BSP in human breast cancer invasion and metastasis, the full-length BSP cDNA was transfected into the MDA-MB-231-BAG human breast cancer cell line under the control of the CMV promoter. Clones expressing BSP and vector control clones were isolated. BSP producing clones showed increased monolayer wound healing, a faster rate of stellate outgrowth in Matrigel and increased rate of invasion into a collagen matrix when compared to control clones. Clones were also examined in models of breast cancer growth and metastasis in vivo. BSP transfected clones showed an increased rate of primary tumor growth following mammary fat pad injection of nude mice. BSP transfected clones and vector control clones metastasized to soft organs and bone at a similar rate after intra-cardiac injection as determined by real-time PCR and X-ray analysis. Although these organs were targets for both BSP transfected and non-transfected cells, the size of the metastatic lesion was shown to be significantly larger for BSP expressing clones. This was determined by real-time PCR analysis for soft organs and by X-ray analysis of bone lesions. For bone this was confirmed by intra-tibial injections of cells in nude mice. We conclude that BSP acts to drive primary and secondary tumor growth of breast cancers in vivo.
我们研究了骨唾液蛋白（BSP）在乳腺癌进展中的作用，BSP是一种通常在骨中发现的分泌型糖蛋白。为了探究BSP在人类乳腺癌侵袭和转移中的功能，将全长BSP cDNA在巨细胞病毒（CMV）启动子的控制下转染到MDA-MB-231-BAG人乳腺癌细胞系中。分离出表达BSP的克隆和载体对照克隆。与对照克隆相比，产生BSP的克隆显示单层伤口愈合增加、在基质胶中星状生长速率加快以及侵入胶原基质的速率增加。还在体内乳腺癌生长和转移模型中对克隆进行了检测。在裸鼠乳腺脂肪垫注射后，转染BSP的克隆显示原发性肿瘤生长速率增加。通过实时聚合酶链反应（PCR）和X射线分析确定，转染BSP的克隆和载体对照克隆在心脏内注射后转移到软组织器官和骨的速率相似。尽管这些器官是转染BSP和未转染细胞的靶器官，但对于表达BSP的克隆，转移灶的大小显示明显更大。这通过对软组织器官的实时PCR分析和对骨病变的X射线分析确定。对于骨，通过在裸鼠胫骨内注射细胞得到了证实。我们得出结论，BSP在体内可驱动乳腺癌的原发性和继发性肿瘤生长。
