Tumor Microenvironment and Metastasis Program

摘要，肿瘤微环境和转移计划（TMM） 肿瘤微环境和转移计划（TMM）是一个高度互动的计划，其中成员 联合收割机的基础，基础研究的专业知识，以了解癌细胞自主作用的生物学， 与旁分泌作用和原发灶内肿瘤微环境（TME）的特定成分的关系 肿瘤和远处转移部位，并研究这些相互作用的全身效应。的基础工作 TMM主要用于“实体”肿瘤，反映了HHM进行的“液体肿瘤”基础研究， 提供了通过与临床合作将他们的发现转化为临床的背景， EDT和CPC的翻译成员。了解TME释放到系统中的因素 循环将提供新的诊断策略，而了解TME如何培养癌细胞， 增强侵袭性和各自的临床后遗症，将导致新的癌症预防和治疗 战略布局TMM的目标是将实体瘤病理生物学的发现转化为TME， 转移到新的癌症靶点和新的治疗方法的全身效应，以防止转移， 后遗症TMM通过关注两个首要主题来推进这一愿景：主题1关注癌症 细胞-基质相互作用及其在癌症发生、发展和转移中的作用。这些相互作用 涉及TME组分，例如癌症相关的成纤维细胞，髓源性抑制细胞， 巨噬细胞、T和B淋巴细胞以及细胞外基质;主题2包括 转移以及导致肌肉、骨骼和认知功能紊乱的机制， 各自的临床后遗症在过去五年中，取得了一些显著的成功，包括 由Wade Clapp博士的工作领导的过度活跃Ras信号传导的SPORE的资金， 胰腺癌、卵巢癌和前列腺癌工作组，增加了这些领域的资金; 以及对癌症转移对肌肉骨骼影响的新见解。前乳房的几个成员 癌症计划被纳入TMM，以加强实体癌的研究专业知识。务虚会福斯特 集中、深入的合作。TMM接待了来访的专家并招募了具有专业知识的教职员工 根据年度务虚会上确定的需要。TMM有28个正式成员和8个准成员，代表17个 印第安纳大学医学院的各系和5所学校，印第安纳州大学- 印第安纳波利斯普渡大学（IUPUI）和IU布卢明顿。该计划的直接资金总额为910万美元（20%）， 自2013年以来增加），以及680万美元的同行评审资金，其中240万美元来自NCI，180万美元来自其他NIH 院所在过去的资助期内，TMM成员撰写了394篇出版物（18%是内部出版物）。 方案，26%的跨方案，64%的机构间合作），并有17个多PI赠款 包括6个机构间和8个方案间（EDT-5、HHM-2和CPC-1），反映出 通过地方、国家和国际网络开展合作。

ABSTRACT, Tumor Microenvironment and Metastasis Program (TMM) The Tumor Microenvironment and Metastasis Program (TMM) is a highly interactive Program in which members combine basic, fundamental research expertise to understand the biology of cancer cell autonomous effects in relation to paracrine actions and specific components of the tumor microenvironment (TME) within the primary tumor and at distant metastatic sites and to study the systemic effects of those interactions. The basic work of TMM in predominately “solid” tumors mirrors the basic research in “liquid tumors” conducted by HHM which provides the backdrop for translating their findings into the clinic through collaborations with the clinical and translational members of EDT and CPC. Understanding the factors released by the TME into the systemic circulation will provide novel diagnostic strategies, whereas understanding how the TME nurtures cancer cells to enhance invasion and the respective clinical sequelae, will lead to new cancer prevention and treatment strategies. The goals of TMM are to translate discoveries of the pathobiology of solid tumors, the TME, and systemic effects of metastases into new cancer targets and novel therapies, so as to prevent metastases and sequelae. TMM advances this vision by focusing on two overarching themes: Theme 1 is focused on cancer cell-stroma interactions and their roles in cancer initiation, progression, and metastasis. These interactions involve TME components such as cancer-associated fibroblasts, myeloid derived suppressor cells, macrophages, T and B lymphocytes and the extracellular matrix; Theme 2 encompasses the systemic effects of metastases and the mechanisms that contribute to perturbations in muscle, bone and cognitive functions and respective clinical sequelae. During the past five years, there have been several notable successes, including the funding of a SPORE in hyperactive Ras signaling led by work of Dr. Wade Clapp, further development of working groups in cancers of the pancreas, ovary, and prostate, resulting in increased funding in these areas; and new insight into musculoskeletal effects of cancer metastasis. Several members from the former Breast Cancer Program were incorporated into TMM to enhance research expertise in solid cancers. Retreats foster focused, in depth collaborations. TMM has hosted visiting experts and recruited faculty members with expertise based on needs identified at the annual retreats. TMM has 28 Full and 8 Associate Members, representing 17 Departments and 5 Schools on the campuses of Indiana University School of Medicine, Indiana University- Purdue University Indianapolis (IUPUI), and IU Bloomington. The Program has $9.1M in total direct funding (20% increase since 2013), and $6.8M in peer-reviewed funding, with $2.4M from the NCI and $1.8M from other NIH Institutes. Over the past funding period, TMM members have authored 394 publications (18% intra- programmatic, 26% inter-programmatic, and 64% inter-institutional collaborations) and have 17 multi-PI grants including six inter-institutional and eight inter-programmatic (EDT-5, HHM-2 and CPC-1) reflecting strong collaborations through local, national and international networking.