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Investigating the Role of Local Paracrine Wnt signaling in Adrenal Cancer

Semester: Summer 2023

Presentation description

The Wnt signaling pathway plays an important role in development and homeostasis, and is aberrantly activated in many human cancers. Wnt signaling is comprised of the canonical pathway, mediated through beta catenin, and the non-canonical pathway, mediated through various ligands. The adrenal gland is highly dependent on Wnt signaling for normal growth and aberrant Wnt activation is a hallmark of adrenal cancer. We found that high expression of WNT5A is associated with a poor prognosis in adrenal cancer patients. WNT5A is a ligand that can activate downstream signaling, and although it's role in promoting tumor progression is poorly understood, it has been shown to be involved in immune regulation. Therefore, we hypothesized that paracrine WNT5A signaling represses myeloid cell recruitment to support tumor progression. To test this hypothesis, we used a conditional genetic knockout mouse model (SF1:Znrf3 cKO) representative of adrenal cancer, and a double knockout mouse model (SF1:Znrf3;Wnt5a dKO). In our Znrf3 cKO mice, we previously found females have higher expression of the Wnt5a transcript and therefore we focused our studies on females only. Initially we found adrenal weight to be significantly decreased in the dKO compared to cKO at early (9-week) and late (24-week) timepoints. Next, we evaluated immune infiltration using CD68 (myeloid marker) staining at both timepoints, and no significant difference in the number CD68-positive cells was found between Znrf3 cKO or Znrf3;Wnt5a dKO mice. However, there was an apparent difference in the number of fused myeloid clusters. We quantified this by cell size and found the size of CD68-positive cells was higher at 9- (1.17-fold increase, P<.001) and 24-weeks (1.41-fold increase, P=.015). Overall, this decrease in adrenal weight and increase in fused clusters suggests Wnt5a may play a role in mediating phagocytosis or myeloid cell function. Further understanding of this mechanism may provide novel insight into how Wnt signaling contributes to tumor progression through modulation of the surrounding myeloid environment.

Presenter Name: Guadalupe Castañeda-Hernandez

Presentation Type: Poster
Presentation Format: In Person
Presentation #61
College: Medicine
School / Department: Oncological Sciences
Research Mentor: Kaitlin Basham
Date | Time: Thursday, Aug 3rd | 10:30 AM