权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Role of the smooth muscle layer in bladder cancer biology and progression: a systems and experimental approach

平滑肌层在膀胱癌生物学和进展中的作用：系统和实验方法

基本信息

批准号：
10527880
负责人：
Ashley Marie Laughney
金额：
$ 37.41万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-12 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10527880
关键词：
Address Affect Basement membrane Behavior Biological Biomechanics Bladder Neoplasm Cancer Biology Carcinoma Cell Communication Cells Cessation of life Characteristics Clinical Coculture Techniques Computer Analysis Cystectomy Data Dependence Development Distant Metastasis Epithelial Event Formalin Freezing Genetic Transcription Heterogeneity High Prevalence Homo Immunohistochemistry Investigation Knowledge Lead Location Malignant Neoplasms Malignant neoplasm of urinary bladder Maps Mediating Mesenchymal Muscle Neoplasm Metastasis Organ Organogenesis Organoids Paraffin Embedding Pathway interactions Patient-Focused Outcomes Patients Phenotype Predictive Value Prognosis Proteomics Resolution Role Sampling Signal Pathway Signal Transduction Smooth Muscle Smooth Muscle Myocytes Smooth Muscle Tumor Source System Technology Testing Tissue Embedding Tumor Cell Invasion Tumor-Derived Validation autocrine base cancer cell cell behavior cell type cellular targeting cohort computerized tools genome-wide innovation insight interest lymph nodes muscle invasive bladder cancer neoplastic cell new therapeutic target novel paracrine phosphoproteomics prognostic value receptor response single-cell RNA sequencing therapeutic target transcriptome transcriptomics tumor tumor microenvironment tumor progression virtual

项目摘要

PROJECT SUMMARY Carcinomas are the most common cancers. In tumors arising in hollow organs, two major events during tumor progression are disruption of the basement membrane and invasion of the smooth muscle layer. In bladder cancer, muscle-invasion is associated with lymph node and distant metastases and poor prognosis. Despite extensive interest in the tumor microenvironment, virtually nothing is known about how tumor cells and smooth muscle cells (SMC) interact. Preliminary observations support our central hypothesis that the smooth muscle layer may promote, rather than restrain, tumor progression and that it can impact on the tumor cell phenotype in a context- dependent manner. We aim to address this significant knowledge gap through a top-down systems and bottom-up experimental approach. In Aim 1, we propose combining high-throughput and spatially-resolved single cell expression profiling with innovative computational analyses of cell-cell interactions in samples from patients with muscle-invasive bladder cancer to identify cellular interactions that modulate tumor cell phenotype at the muscle-invasive front. Special emphasis will be placed on interrogating tumor cell-SMC crosstalk at this interface, although all autocrine and paracrine interactions will be analyzed at a systems level in an unbiased fashion. In Aim 2, we propose using co-culture systems to mechanistically dissect tumor cell-SMC crosstalk, including identifying transcriptomic changes induced by SMC on tumor cells, determining whether this cross- talk is mediated by contact or soluble factors, and identifying candidate pathways that underlie this effect for downstream validation. The amalgamation of these approaches will reveal markers of SMC activation with prognostic and/or predictive value and may lead to the discovery of new therapeutic targets for muscle-invasive bladder cancer. We expect to uncover a yet unexplored role of the tumor microenvironment in bladder cancer phenotypes and progression.

项目总结

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Tumor and Stromal Cell Targeting with Nintedanib and Alpelisib Overcomes Intrinsic Bladder Cancer Resistance.

尼达尼布和 Alpelisib 靶向肿瘤和基质细胞克服了膀胱癌的内在抵抗力。

DOI：
10.1158/1535-7163.mct-21-0667
发表时间：
2023
期刊：
Molecular cancer therapeutics
影响因子：
5.7
作者：
Marqués,Miriam;Corral,Sonia;Sánchez-Díaz,María;DelPozo,Natalia;MartínezdeVillarreal,Jaime;Schweifer,Norbert;Zagorac,Ivana;Hilberg,Frank;Real,FranciscoX
通讯作者：
Real,FranciscoX

Predictive signature of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer integrating mRNA expression, taxonomic subtypes, and clinicopathological features.