Expression of Connexins in Normal and Neoplastic Canine Bone Tissue
Expression of Connexins in Normal and Neoplastic Canine Bone Tissue
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DOI：
10.1354/vp.08-vp-0263-s-fl
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发表时间：
2009-09-01
影响因子：
2.4
通讯作者：
Dagli, M. L. Z.
中科院分区：
文献类型：
--
作者：
Sanches, D. S.;Pires, C. G.;Dagli, M. L. Z.
先前的研究表明，间隙连接的细胞间通讯在骨形成中发挥作用。参与骨组织发育、分化和调节的主要连接蛋白是连接蛋白 (Cx) 43。此外，Cx46 也有表达，主要位于跨高尔基体区域。这些连接蛋白表达模式的改变和异常位置与肿瘤发生有关，表明肿瘤组织中间隙连接细胞间通讯（GJIC）能力缺陷。在本研究中，我们通过免疫荧光评估了正常和肿瘤骨组织中 Cx43 和 Cx46 的表达，通过实时 PCR 评估了这些连接蛋白的基因表达，及其与细胞增殖指数和胶原蛋白沉积的相关性。研究人员对 14 例骨肿瘤病变进行了研究，其中包括 13 例骨肉瘤和 1 例骨多小叶肿瘤。正常骨组织和肿瘤骨组织之间的 Cx43 mRNA 水平相似。在正常骨组织中，Cx43蛋白主要存在于细胞间膜中。然而，在这里研究的所有骨肿瘤中，Cx43 都存在于细胞膜中，并且异常地存在于细胞质中。仅就肿瘤样本而言，我们确定了 Cx43 表达与细胞增殖之间可能存在负相关，尽管也注意到 Cx43 表达与胶原沉积之间存在正相关。相反，与正常骨相比，Cx46 在肿瘤骨组织中的表达水平较低，并且被发现保留在核周区域。尽管这两种连接蛋白在肿瘤组织与正常组织中的表达存在差异，但我们得出结论，这些连接蛋白在正常和肿瘤狗骨组织中的亚细胞位置存在差异，并表明这些发现与细胞增殖和可能分化的某些方面之间可能存在相关性。
Previous studies showed that intercellular communication by gap junctions has a role in bone formation. The main connexin involved in the development, differentiation, and regulation of bone tissue is connexin (Cx) 43. In addition, Cx46 is also expressed, mostly localized within the trans-Golgi region. Alterations in the expression pattern and aberrant location of these connexins are associated with oncogenesis, demonstrating a deficient gap junctional intercellular communication (GJIC) capacity in neoplastic tissues. In this study, we evaluated normal and neoplastic bone tissues regarding the expression of Cx43 and Cx46 by immunofluorescence, gene expression of these connexins by real-time PCR, and their correlation with cell proliferation index and deposition of collagen. Fourteen neoplastic bone lesions, including 13 osteosarcomas and I multilobular tumor of bone, were studied. The mRNA levels of Cx43 were similar between normal and neoplastic bone tissue. In normal bone tissue, the Cx43 protein was found mainly in the intercellular membranes. However, in all bone tumors studied here, the Cx43 was present in both cell membranes and also aberrantly in the cytoplasm. Regarding only tumor samples, we determined a possible inverse correlation between Cx43 expression and cellular proliferation, although a positive correlation between Cx43 expression and collagen deposition was also noted. In contrast, Cx46 had lower levels of expression in neoplastic bone tissues when compared with normal bone and was found retained in the perinuclear region. Even though there are differences between these two connexins regarding expression in neoplastic versus normal tissues, we concluded that there are differences regarding the subcellular location of these connexins in normal and neoplastic dog bone tissues and suggest a possible correlation between these findings and some aspects of cellular proliferation and possibly differentiation.