Tumor metastasis: Biobehavioral mechanisms

肿瘤转移：生物行为机制

• 批准号: 7847325
• 负责人: ANIL K SOOD
• 金额: $ 30.84万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-24 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7847325
• 关键词: Affect; Anoikis; Apoptosis; Ascites; Behavioral; Bombesin; Catecholamines; Cell Survival; Cell-Matrix Junction; Cells; Chronic stress; Cytoprotection; Data; Down-Regulation; Employee Strikes; Epinephrine; Extracellular Matrix; Focal Adhesion Kinase 1; Funding; Goals; Growth; Hormones; Human; Immunity; In Vitro; Invaded; Investigation; Lead; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of ovary; Mediating; Neoplasm Metastasis; Neuropeptides; Neurosecretory Systems; Norepinephrine; Normal Cell; Oncogenes; Ovarian Carcinoma; PTEN gene; Pathway interactions; Play; Process; Psychosocial Factor; Psychosocial Stress; Ras/Raf; Receptor Protein-Tyrosine Kinases; Recovery; Research; Resistance; Role; Signal Pathway; Site; Stress; TP53 gene; Therapeutic; Time; Tumor Suppressor Genes; United States National Institutes of Health; Work; abstracting; base; beta-adrenergic receptor; biobehavior; cancer cell; in vitro Assay; in vivo; inhibitor/antagonist; migration; mouse model; neoplastic cell; neurochemistry; novel; overexpression; parent grant; protective effect; public health relevance; tumor; tumor growth; tumor progression

DESCRIPTION (provided by applicant): Abstract In reference to NOT-OD-09-058 (Notice Title: NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications), we submit this Competitive Revision to the parent grant entitled "Tumor metastasis: Biobehavioral mechanisms (R01CA110793)." Psychosocial stress can elicit alterations of immunological, neurochemical, and endocrinological functions. To date, most of the research dealing with stress and tumor growth has focused on suppressed immunity; however, progressive growth of cancer is influenced by many other factors including tumor cell migration and invasion. There has been little investigation of the effect of stress hormones such as norepinephrine and epinephrine on these key processes that are required for metastasis. Focal adhesion kinase (FAK) is one of the key factors involved in tumor cell migration and invasion. We have compelling preliminary data that one of the stress hormones, norepinephrine, can directly activate FAK and promote tumor growth and these effects can be blocked by using inhibitors of beta-adrenergic receptors. Furthermore, our preliminary data suggest that FAK plays a key role in ovarian cancer migration and invasion. The parent grant has determined the underlying mechanisms and pathways by which stress hormones can affect ovarian cancer migration and invasion using in vitro assays and we have experimentally identified the in vivo effects of chronic stress on ovarian cancer progression using a well-characterized mouse model of ovarian carcinoma and are examining the associations between psychosocial factors and FAK in human ovarian cancers. During this work, we have made novel observations that chronic stress and associated increases in catecholamines protect tumor cells from undergoing anoikis, but the exact mechanisms are not well known. In the present supplement, we seek to determine whether chronic stress and associated neuroendocrine dynamics could protect ovarian cancer cells from anoikis, and to identify the underlying signaling pathways. The proposed supplement will advance the goals and objectives of the parent grant by allowing us to examine in vitro mechanisms of norepinephrine mediated protective effects against anoikis and determine in vivo effects of stress on protection of tumor cells in ascites against apoptosis (in vivo reflection of anoikis avoidance by tumor cells). Findings of this study could lead to identification of a completely new mechanism by which chronic stress affects tumor cell survival and growth, and therefore may lead to new behavioral and pharmacological therapeutic approaches. PUBLIC HEALTH RELEVANCE: Project narrative FAK is known to promote tumor cell survival and may play a significant role in avoidance of anoikis. We have previously demonstrated that catecholamines promote ovarian carcinoma growth via stimulation of angiogenic pathways. However, the mechanism by which invading tumor cells survive anoikis remains largely unknown. The proposed work here will advance the goals and objectives of the parent grant by allowing us to examine in vitro mechanisms of norepinephrine mediated protective effects against anoikis and determine in vivo effects of stress on FAK and Src and protection of cells in ascites against apoptosis (in vivo reflection of anoikis avoidance by tumor cells).

描述(由申请人提供)：摘要参考NOT-OD-09-058(通知标题：美国国立卫生研究院宣布恢复法资金可用于竞争性修订申请)，我们将此竞争性修订提交给名为“肿瘤转移：生物行为机制(R01CA110793)”的母公司拨款。心理社会应激可引起免疫、神经化学和内分泌功能的改变。到目前为止，关于应激与肿瘤生长的研究大多集中在免疫抑制方面；然而，肿瘤的进行性生长受到许多其他因素的影响，包括肿瘤细胞的迁移和侵袭。关于去甲肾上腺素和肾上腺素等应激激素对肿瘤转移所需的这些关键过程的影响的研究很少。粘着斑激酶(FAK)是参与肿瘤细胞迁移和侵袭的关键因子之一。我们有令人信服的初步数据表明，应激激素之一去甲肾上腺素可以直接激活FAK，促进肿瘤生长，这些作用可以通过使用β-肾上腺素能受体的抑制剂来阻断。此外，我们的初步数据表明，FAK在卵巢癌的转移和侵袭中起着关键作用。父母的资助已经通过体外分析确定了应激激素影响卵巢癌迁移和侵袭的潜在机制和途径，我们已经通过实验确定了慢性应激对卵巢癌进展的体内影响，并正在研究心理社会因素与人类卵巢癌FAK之间的联系。在这项工作中，我们进行了新的观察，发现慢性应激和相关儿茶酚胺的增加可以保护肿瘤细胞免受失巢凋亡的影响，但确切的机制尚不清楚。在本补充资料中，我们试图确定慢性应激和相关的神经内分泌动力学是否可以保护卵巢癌细胞免受失巢凋亡的影响，并确定潜在的信号通路。建议的补充将通过允许我们在体外研究去甲肾上腺素介导的抗失巢凋亡的保护作用的机制，并在体内确定应激在保护腹水中的肿瘤细胞免受凋亡的影响(体内反映肿瘤细胞对失巢凋亡的避免)，来推进父母赠款的目标和目的。这项研究的发现可能导致识别一种全新的机制，通过这种机制，慢性应激影响肿瘤细胞的生存和生长，从而可能导致新的行为和药物治疗方法。 公共卫生相关性：项目叙事FAK已知可以促进肿瘤细胞存活，并可能在避免失巢死亡方面发挥重要作用。我们以前已经证明，儿茶酚胺通过刺激血管生成途径促进卵巢癌的生长。然而，侵袭性肿瘤细胞存活失巢的机制在很大程度上仍不清楚。这项拟议的工作将推进父母赠款的目标和目标，使我们能够在体外研究去甲肾上腺素介导的抗失巢凋亡效应的机制，并在体内确定应激对FAK和Src的影响以及对腹水中细胞凋亡的保护(体内反映肿瘤细胞对失巢凋亡的避免)。

项目成果

A biobehavioral perspective of tumor biology.

肿瘤生物学的生物行为视角。

• 发表时间: 2005
• 期刊: Discovery medicine
• 影响因子: 1.4
• 作者: McDonald,PaigeGreen;Antoni,MichaelH;Lutgendorf,SusanK;Cole,StevenW;Dhabhar,FirdausS;Sephton,SandraE;Stefanek,Michael;Sood,AnilK
• 通讯作者: Sood,AnilK

Depressive symptoms and cortisol rhythmicity predict survival in patients with renal cell carcinoma: role of inflammatory signaling.

• DOI: 10.1371/journal.pone.0042324
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Cohen L;Cole SW;Sood AK;Prinsloo S;Kirschbaum C;Arevalo JM;Jennings NB;Scott S;Vence L;Wei Q;Kentor D;Radvanyi L;Tannir N;Jonasch E;Tamboli P;Pisters L
• 通讯作者: Pisters L