Investigating Breast Cancer Collective Invasion

描述（由申请方提供）：在肿瘤进展期间，由于过度增殖细胞在导管和小叶的管腔空间中积聚，乳腺的良好有序结构被破坏。 随着时间的推移，肿瘤细胞可以侵入基质，在那里它们可以进入脉管系统并扩散到整个身体的远端部位。 虽然诱导侵袭性生长是转移级联反应中的关键步骤，但乳腺癌细胞如何变得具有侵袭性仍然知之甚少。 使用器官型培养系统和动物模型，我们建议确定（1）细胞运动性是如何调节细胞内信号通路在集体入侵;（2）乳腺成纤维细胞如何诱导集体入侵和（3）肿瘤细胞亚群如何触发集体入侵。 破译乳腺癌侵袭的要求可以确定肿瘤和微环境中治疗干预的靶点。

DESCRIPTION (provided by applicant): During tumor progression the well-ordered architecture of the mammary gland becomes disrupted as hyperproliferative cells accumulate in the luminal space of ducts and lobules. Over time the neoplastic cells can invade into the stroma where they can access the vasculature system and disseminate to distant sites throughout the body. Although the induction of invasive growth is a key step in the metastatic cascade, how breast cancer cells become invasive remains poorly understood. Using an organotypic culture system and animal models we propose to determine (1) how cell motility is regulated by intracellular signaling pathways during collective invasion; (2) how mammary fibroblasts induce collective invasion and (3) how subpopulations of neoplastic cells trigger collective invasion. Deciphering the requirements for breast cancer invasion could identify targets for therapeutic intervention in both the tumor and the microenvironment.