三维微环境中不同分子对乳腺癌细胞骨转移的化学引诱特性研究

Gulben Avsar, B. Zeybek, Aylin Sendemir-rkmez
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摘要

转移是癌症最具破坏性的一步,它被定义为肿瘤细胞从原发肿瘤细胞转移到其他器官。由于骨转移的分子和细胞机制尚不清楚,开发有效的治疗方法是不可能的。骨细胞外基质中某些分子的化学引诱特性被认为是转移的可能原因之一。在这项研究中,通过静电纺丝法模拟天然多孔骨结构制备胶原蛋白支架,以了解转移性乳腺癌细胞骨转移中可能常见的化学引诱分子。研究了MCF-7转移性乳腺癌细胞在骨桥蛋白、I型胶原和羟基磷灰石功能化表面和支架上的粘附动力学。三维趋化载玻片用于可视化迁移。细胞粘附动力学和迁移结果均表明,1型胶原和羟基磷灰石联合作为化学引诱剂在乳腺癌细胞骨转移中比单独使用1型胶原更有效。骨桥蛋白引起的迁移和细胞粘附相对于I型胶原较多;结果表明,该蛋白在乳腺癌骨转移过程中是一种有效的化学引诱剂。研究表明,骨矿物质的微环境支持肿瘤细胞在骨内的生长和定植,在转移生态位的形成中起着重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Investigation of chemoattractant properties of various molecules in three-dimensional microenvironment to metastasis of breast cancer cells to bone
Metastasis is the most destructive step of cancer and it is defined as spreading of tumor cells from the primary tumor cite to other organs. Because of the fact that the molecular and cellular mechanisms underlying bone metastasis have not been yet understood, the development of an effective therapy is not possible. Chemo-attractant properties of some molecules in the bone extracellular matrix has been considered among possible reasons of metastasis. In this study, collagen scaffolds were produced by electrospinning method mimicking natural porous bone structure to understand possible chemo-attractant molecules that are common in bone metastases of metastatic breast cancer cells. MCF-7 metastatic breast cancer cells' adhesion kinetics were studied on the surfaces and scaffolds which are functionalized by osteopontin, collagen type I and hydroxyapatite. Three dimensional chemotaxis slides were used for visualizing the migration. Both cell adhesion kinetics and migration results showed that collagen type 1 and hydroxyapatite combination was more effective as a chemo-attractant than only collagen type 1 in the bone metastasis of breast cancer cells. Osteopontin caused migration and cell adhesion relatively more than collagen type I; and it was showed that this protein is an effective chemo-attractant in the bone metastasis of breast cancer cells. It was shown that micro environments of the bone minerals play an important role in the formation of metastatic niche because of their support to the development and colonization of tumor cells in the bone.
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