Extracellular Matrix in Renal Development and Cancer

Presented at: Cell Biology 2020
C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Senior Postdoctoral Research Fellow, GOFARR Laboratory for Organ Regenerative Research and Cell Therapeutics in Urology, Children's Hospital Los Angeles
    BIOGRAPHY

Abstract

The extracellular matrix (ECM) is a three-dimensional structure that provides physical support for tissues/organs and biochemical/biomechanical cues for tissue morphogenesis, differentiation, and homeostasis. The continual remodeling (degradation/new synthesis) of the ECM is crucial for tissue homeostasis, development, and injury processes and contributes/regulates tumor malignancy, growth, and patient response to cancer treatment. Recent evidence shows that Wilms’ tumor (WT), pediatric cancer that accounts for 95% of the renal malignancies in children, could be considered an aberrant nephrogenesis, where nephron progenitors (NP) expressing SIX2 and CITED1  proliferate uncontrollably, hampering terminal differentiation into functional mature nephron structures. We have characterized via transcriptomic analysis and immunohistochemistry the composition of the ECM within the WT-NP and determine its role in cancer development, and identified how modulation of ECM proteins and their receptors in the NP niche might favor self-renewal vs. differentiation. We show that by altering the NP niche, we could promote NP self-renewal maintenance and hampered differentiation. Our data suggest that ECM secreted by cancerous NP promotes tumor development and growth, thus targeting ECM remodeling processes might be essential for the development of innovative treatment specifically designed to halt WT progression, particularly in patients with severe prognosis or recurrences.

Learning Objectives:

1. Identify the ECM composition in Wilms’ tumor

2. Identify how variation in the Wilms’ tumor nephron progenitor niche may promote continuous self-renewal and hamper differentiation


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