Receptor Cross-Talk in Early Metastatic Dissemination

早期转移性播散中的受体串扰

• 批准号: 10355901
• 负责人: Mary Sharon Stack
• 金额: $ 21.95万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10355901
• 关键词: Abdomen; Address; Advanced Glycosylation End Products; Age; Aging; Architecture; Ascites; Benchmarking; Biological; Biological Models; Biomechanics; Biosensing Techniques; Cancer Etiology; Cell Adhesion; Cell Aging; Cell Communication; Cessation of life; Collagen; Communication; Complex; Coupled; Cytolysis; Data; Diagnosis; Disease; Disease Progression; Disseminated Malignant Neoplasm; Evaluation; Event; Funding; Goals; Grant; Greater sac of peritoneum; Human; In Vitro; Incidence; Intervention; Intra-abdominal; Knock-out; Laboratories; Ligands; Link; Liquid substance; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Mediating; Mediator of activation protein; Mesothelial Cell; Metastatic to; MicroRNAs; Microfluidics; Molecular; Molecular Analysis; Mus; Neoplasm Metastasis; Orphan; Pain; Pathway interactions; Pattern; Peritoneal; Peritoneal Mesothelial Cell; Peritoneal lavage; Prognosis; Property; Protein-Lysine 6-Oxidase; Publishing; Quantitative Reverse Transcriptase PCR; ROR1 gene; Receptor Cross-Talk; Receptor Protein-Tyrosine Kinases; Regulation; Research; Risk Factors; Role; Structure; Survival Rate; Technology; Time; Tissues; Tumor Burden; Validation; Woman; age effect; age related; aged; base; biophysical properties; cancer cell; cell behavior; crosslink; epidemiologic data; exosome; experimental study; imaging modality; implantation; in vivo; in vivo Model; innovation; insight; intraperitoneal; miRNA expression profiling; mortality; nanopore; neoplastic cell; new technology; new therapeutic target; novel; nucleic acid detection; parent grant; programs; receptor; solid state; success; tumor; tumor microenvironment

ABSTRACT Ovarian cancer (OvCa) is the most fatal gynecologic cancer with a low (<27%) 5-year survival rate. Survival of women with OvCa has not changed appreciably in over 30 years and most women diagnosed will die of painful complications that arise as a result of widely disseminated intraperitoneal (IP) metastasis. Epidemiologic data indicate that age is a significant independent risk factor for OvCa incidence; however disease progression in the aged host has not been examined experimentally. Experiments in the parent grant address the hypothesis that host aging induces changes in peritoneal structure and function that influence tumor cell adhesion, matrix anchoring, and ultimate metastatic success. Ongoing studies in Aim 1 examine age-induced changes in peritoneal mesothelial cells (MCs) and the resulting impact on MC receptivity to metastatic implantation; Aim2 focuses on aging of the sub-MC collagen matrix, evaluation of aging-induced changes in matrix crosslinking and biophysical properties, and the influence on metastatic anchoring; and Aim3 investigates Wnt5a as a mediator of tumor:host cross-talk in the aging peritoneal cavity. In this ‘revision’ grant, we propose to add a new aim to the parent grant to employ novel technology developed through support from the NCI Innovative Molecular Analysis Technologies (IMAT) program. This research, conducted by Dr. H-C Chang, developed a novel solid-state nanopore technology for isolation and lysis of exosomes from complex biofluids and capture and quantitation of exosomal microRNAs. Using this technology, the new Aim 4 of the revision application will assess the role of bi-directional tumor:host communication via exosome-mediated miRNA delivery in metastatic progression in the context of host aging. Successful completion of the proposed experiments will provide rigorous functional validation and benchmarking of the solid-state nanopore technology in an interesting and relevant model system. Simultaneously we will enhance the impact of the parent grant and provide unprecedented insight into molecules and events that mediate tumor:host communication in the aged host.

抽象的 卵巢癌（OVCA）是最致命的妇科癌症（<27％）的5年生存率 有OVCA的妇女在30多年中没有明显改变，大多数被诊断出的妇女会死于痛苦 由于广泛传播的腹膜内（IP）转移而产生的并发症 表明年龄是OVCA发病率的重要独立危险因素； 实验中的老年寄主是在父母赠款中进行的。 宿主老化的腹膜结构和功能变化会影响肿瘤细胞粘附，矩阵 锚定，最终的转移性成功。 腹膜间皮细胞（MC）和对MC接收到转移植入的影响 侧重于亚MC胶原蛋白基质的老化，评估基质交联的衰老变化 生物物理特性，以及对转移性锚定的影响； 肿瘤的中介：在此“修订”授予的衰老腔腔中的宿主交叉言论。 向父母赠款的新目标采用通过NCI创新的支持而开发的新技术 分子分析技术（IMAT）计划。 新型的固态纳米孔纳米孔技术，用于隔离和裂解复杂生物流体的外泌体并捕获 使用此技术的外泌体microRNA的定量 评估双向肿瘤的作用：通过内泌体介导的miRNA传递在转移性中的宿主通信 在宿主衰老的背景下的进展。 在有趣且 相关模型系统。 对介导肿瘤的分子和事件的前所未有的见解：老年宿主的宿主通信。

项目成果

Lipid Regulatory Proteins as Potential Therapeutic Targets for Ovarian Cancer in Obese Women.

• DOI: 10.3390/cancers12113469
• 发表时间: 2020-11-21
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Yang J;Stack MS
• 通讯作者: Stack MS

Wnt5a Signaling in Cancer.

• DOI: 10.3390/cancers8090079
• 发表时间: 2016-08-26
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Asem MS;Buechler S;Wates RB;Miller DL;Stack MS
• 通讯作者: Stack MS

Obesity Contributes to Ovarian Cancer Metastatic Success through Increased Lipogenesis, Enhanced Vascularity, and Decreased Infiltration of M1 Macrophages.

• DOI: 10.1158/0008-5472.can-15-0706
• 发表时间: 2015-12-01
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Liu Y;Metzinger MN;Lewellen KA;Cripps SN;Carey KD;Harper EI;Shi Z;Tarwater L;Grisoli A;Lee E;Slusarz A;Yang J;Loughran EA;Conley K;Johnson JJ;Klymenko Y;Bruney L;Liang Z;Dovichi NJ;Cheatham B;Leevy WM;Stack MS
• 通讯作者: Stack MS

An ion-exchange nanomembrane sensor for detection of nucleic acids using a surface charge inversion phenomenon.

• DOI: 10.1016/j.bios.2014.04.008
• 发表时间: 2014-10-15
• 期刊: BIOSENSORS & BIOELECTRONICS
• 影响因子: 12.6
• 作者: Senapati, Satyajyoti;Slouka, Zdenek;Shah, Sunny S.;Behura, Susanta K.;Shi, Zonggao;Stack, M. Sharon;Severson, David W.;Chang, Hsueh-Chia
• 通讯作者: Chang, Hsueh-Chia

Epidermal growth factor receptor-mediated membrane type 1 matrix metalloproteinase endocytosis regulates the transition between invasive versus expansive growth of ovarian carcinoma cells in three-dimensional collagen.

表皮生长因子受体介导的膜 1 型基质金属蛋白酶内吞作用调节三维胶原蛋白中卵巢癌细胞侵袭性生长与扩张性生长之间的转变。

• DOI: 10.1158/1541-7786.mcr-08-0571
• 发表时间: 2009
• 期刊: Molecular cancer research : MCR
• 作者: Moss,NatalieM;Liu,Yueying;Johnson,JeffJ;Debiase,Philip;Jones,Jonathan;Hudson,LaurieG;Munshi,HidayatullahG;Stack,MSharon
• 通讯作者: Stack,MSharon