Please enable JavaScript or talk to your local administrator to get JavaScript enabled.

Project

Exosomes: A novel mechanism for bladder cancer tumorigenesis and progression

Funder: National Cancer Institute

Funding period
USD 1.8 M
Funding amount
Abstract
DESCRIPTION (provided by applicant): Bladder cancer (BC) is the fifth most commonly diagnosed malignancy in the United States. The majority of BC patients have non-muscle invasive (NMI) disease, and these tumors frequently recur after transurethral resection of initial tumors. Approximately 25-30% of BC patients have muscle invasive disease (MIBC). Unfortunately, 50% of MI BC patients will develop metastatic disease with 10% five year survival rate. This high recurrence rate in NMI BC, and high morbidity and mortality in MI BC make it one of the most burdensome cancers to manage and treat. Therefore, there is a great need for understanding the underlying biology of these tumors which would lead to the development of stage specific therapeutic targets to prevent tumor recurrence and progression. Small extracellular membrane bound vesicles, termed exosomes, can be secreted from numerous types of cells taken up by neighboring cells, consequently affecting their behaviors. There is increasing evidence supporting the theory that cancer exosomes play vital roles in many steps of cancer development and progression. Preliminary studies showed that BC exosomes promote BC cell migration, invasion and angiogenesis. Several BC exosome proteins were identified, among which EDIL-3 is found to be over-expressed in BC exosomes as compared to normal controls, and knocking down EDIL3 reduced cancer exosome-mediated BC cell migration and angiogenesis. Mechanistic studies indicated that EDIL-3 can activate the transmembrane kinases such as FAK and EGFR, consequently inducing a signal cascade to influence cell proliferation and migration. Based on preliminary studies, we hypothesize that BC-derived exosomes, via the paracrine manner that transfers cancer-associated proteins to recipient cells, consequently promote tumor progression. Moreover, urinary exosome protein profiles from BC patients can serve as disease biomarkers. Four Aims are proposed to study exosome roles in BC biology. Aim 1: To delineate underlying mechanisms by which EDIL-3 promotes bladder progression. Aim 2: To study the roles of 8 cancer-associated exosomal proteins on tumor progression. Aim 3: To determine the expression and function of those cancer-associated proteins in urinary exosomes of BC patients. Aim 4: To study cancer exosome ability to promote cancer progression in vivo. Our long-term goal is to understand the biological functions of cancer exosomes and to reveal possible novel treatment targets.
Similar projects All >
Sorted by: Start Date
Project list item
Intravesical delivery of an Fc-enhanced CD40 agonist antibody for the treatment of bladder cancer

Bladder Cancer Advocacy Network to Jeffrey Ravetch, David Knorr

USD 300,000
2020 - 2022
Project list item
Epigenetic regulators of subtype plasticity in bladder cancer

Bladder Cancer Advocacy Network to John Robert Christin

USD 1,700
2020 - 2020
Project list item
Defining NRF2 induced tumor invasion in bladder cancer

Bladder Cancer Advocacy Network to Yuki Kita, William Youngkwan Kim, Bernard Weissman

USD 50,000
2020 - 2021
Project list item
Alpha1H: A Unique Bladder Cancer Therapeutic, Acting with Great Precision

European Commission

USD 2,452,885
2020 - 2022
Project list item
Dissecting myeloid cell-mediated resistance to immune checkpoint blockade in bladder cancer

National Cancer Institute to NINA BHARDWAJ, JUN ZHU, MATTHEW GALSKY

USD 703,400
2020 - 2025

System

Categories
  • FOR (ANZSRC)

    0601 Biochemistry and Cell Biology

  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Cancer

  • RCDC

    Clinical Research

  • RCDC

    Urologic Diseases

  • HRCS HC

    Cancer

  • HRCS RAC

    2.1 Biological and endogenous factors

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science