Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Neoplasia. 2011 May;13(5):393-405. doi: 10.1593/neo.101720.
The progression of ovarian cancer, from cell transformation through invasion of normal tissue, relies on communication between tumor cells and their adjacent stromal microenvironment. Through a natural selection process, an autocrine-paracrine communication loop establishes reciprocal reinforcement of growth and migration signals. Thus, the cancer-activated stromal response is similar to an off-switch-defective form of the normal, universal response needed to survive insult or injury. It is becoming clearer within the cancer literature base that tumor stroma plays a bimodal role in cancer development: it impedes neoplastic growth in normal tissue while encouraging migration and tumor growth in a co-opted desmoplastic response during tumor progression. In this review, we discuss this reciprocal influence that ovarian cancer epithelial cells may have on ovarian stromal cell-reactive phenotype, stromal cell behavior, disrupted signaling networks, and tumor suppressor status in the stroma, within the context of cancer fibroblast studies from alternate cancer tissue settings. We focus on the exchange of secreted factors, in particular interleukin 1β and SDF-1α, between activated fibroblasts and cancer cells as a key area for future investigation and therapeutic development. A better understanding of the bidirectional reliance of early epithelial cancer cells on activated stromal cells could lead to the identification of novel diagnostic stromal markers and targets for therapy.
卵巢癌的进展，从细胞转化到正常组织的浸润，依赖于肿瘤细胞与其相邻的基质微环境之间的通讯。通过自然选择过程，建立了自分泌-旁分泌通讯回路，从而加强了生长和迁移信号的相互增强。因此，癌症激活的基质反应类似于正常、普遍反应的关闭开关缺陷形式，这种反应是为了在受到伤害或损伤时生存。在癌症文献基础中，越来越明显的是，肿瘤基质在癌症发展中起着双重作用：它在正常组织中阻碍肿瘤生长，而在肿瘤进展过程中，通过被募集的纤维化反应促进迁移和肿瘤生长。在这篇综述中，我们讨论了卵巢癌细胞可能对卵巢基质细胞反应表型、基质细胞行为、信号转导网络中断和基质中肿瘤抑制状态的这种相互影响，其背景是来自其他癌症组织环境的癌症成纤维细胞研究。我们专注于激活的成纤维细胞和癌细胞之间分泌因子的交换，特别是白细胞介素 1β 和 SDF-1α，这是未来研究和治疗开发的一个关键领域。更好地理解早期上皮癌细胞对激活的基质细胞的双向依赖关系，可能会导致识别新的诊断性基质标志物和治疗靶点。
