Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model.
Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model.
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DOI：
10.1186/1471-2407-9-45
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发表时间：
2009-02-03
期刊：
影响因子：
3.8
通讯作者：
Mauro LJ
中科院分区：
文献类型：
--
作者：
Schiller KR;Zillhardt MR;Alley J;Borjesson DL;Beitz AJ;Mauro LJ
骨肿瘤微环境包括骨和骨髓腔的正常细胞与来自原发性或转移性癌症的恶性细胞之间的独特相互作用。这种微环境中的大量旁分泌因子，如生长因子TGF-β和趋化因子MCP-1，由许多这些细胞类型分泌。这些因子可以协同作用以调节正常和恶性细胞增殖、恶性细胞迁移和侵袭，并且通常介导骨癌疼痛。虽然存在许多有价值的体外和体内模型，但识别相关的旁分泌因子并破译它们的相互作用仍然是一个挑战。我们的研究的目的是测试一个离体共培养模型，将允许监测的表达，释放和调节的旁分泌因子在一个完整的股骨外植体和肿瘤细胞的相互作用。将完整或骨髓耗尽的新生小鼠股骨和选择的鼠和人肉瘤或癌细胞系单独孵育或在专门的孔板中共培养。通过免疫组化染色、显微镜检查和骨髓细胞计数来确定骨和细胞的活力。ELISA和实时荧光定量RT-PCR检测旁分泌因子的分泌和mRNA表达。骨的复合物在培养物中最多可存活48小时，肿瘤细胞最多可存活4天。骨是TGF-β和MMP 2的主要贡献者，而骨细胞和肉瘤细胞在共培养物中均分泌趋化因子MCP-1。股骨和肉瘤之间的协同相互作用导致MCP-1分泌和表达增强的共培养物，并依赖于骨的造血成分以及其他骨细胞的存在。相反，与乳腺癌细胞共培养导致骨分泌TGF-β和MCP-1减少。这些研究说明了该模型的可行性，以检查完整的骨和肿瘤细胞之间的旁分泌相互作用。使用这种模拟的微环境，将有可能进一步研究不同类型癌症中这些细胞类型之间MCP-1分泌和信号传导的独特调节。
The bone-tumor microenvironment encompasses unique interactions between the normal cells of the bone and marrow cavity and the malignant cells from a primary or metastasized cancer. A multitude of paracrine factors within this microenvironment such as the growth factor, TGF-β, and the chemokine, MCP-1, are secreted by many of these cell types. These factors can act in concert to modulate normal and malignant cell proliferation, malignant cell migration and invasion and, often, mediate bone cancer pain. Although many valuable in vitro and in vivo models exist, identifying the relevant paracrine factors and deciphering their interactions is still a challenge. The aim of our study is to test an ex vivo coculture model that will allow monitoring of the expression, release and regulation of paracrine factors during interactions of an intact femur explant and tumor cells. Intact or marrow-depleted neonatal mouse femurs and select murine and human sarcoma or carcinoma cell lines were incubated singly or in coculture in specialized well plates. Viability of the bone and cells was determined by immunohistochemical stains, microscopy and marrow cytopreps. Secretion and mRNA expression of paracrine factors was quantitated by ELISA and real-time RT-PCR. Compartments of the bone were optimally viable for up to 48 h in culture and tumor cells for up to 4 days. Bone was the major contributor of TGF-β and MMP2 whereas both bone and sarcoma cells secreted the chemokine MCP-1 in cocultures. Synergistic interaction between the femur and sarcoma resulted in enhanced MCP-1 secretion and expression in cocultures and was dependent on the presence of the hematopoietic component of the bone as well as other bone cells. In contrast, coculturing with breast carcinoma cells resulted in reduction of TGF-β and MCP-1 secretion from the bone. These studies illustrate the feasibility of this model to examine paracrine interactions between intact bone and tumor cells. Further study of unique regulation of MCP-1 secretion and signaling between these cell types in different types of cancer will be possible using this simulated microenvironment.
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影响因子：
4.8
作者：
Dallas, SL;Rosser, JL;Bonewald, LF
通讯作者：
Bonewald, LF
影响因子：
5.5
作者：
Cheng, JF;Encarnacion, MMD;Grande, JP
通讯作者：
Grande, JP
影响因子：
6.4
作者：
Ellenrieder, V;Hendler, SF;Gress, TM
通讯作者：
Gress, TM
神经肽 Y 免疫反应性、酪氨酸羟化酶免疫反应性和血管活性肠多肽 - 骨和周围组织中的免疫反应性神经
DOI：
10.1016/0165-1838(88)90016-1
发表时间：
1988-12-01
期刊：
JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM
影响因子：
--
作者：
BJURHOLM, A;KREICBERGS, A;SCHULTZBERG, M
通讯作者：
SCHULTZBERG, M
影响因子：
4
作者：
Morrissey, Colm;Vessella, Robert L.
通讯作者：
Vessella, Robert L.