Kidney Week

Abstract: SA-PO243

A Novel In Vivo Model of Renal Cell Carcinoma (RCC) Angiogenesis

Session Information

• Onconephrology: Immunological Cross-Talk
  November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Onconephrology

• 1700 Onconephrology

Authors

• Levin-Klein, Rena, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Rena Levin-Klein,

• Rabinowitz, Grace, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Grace Rabinowitz,

• Greenberger, Shoshana, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Shoshana Greenberger,

• Beckerman, Pazit, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Pazit Beckerman,

• Pleniceanu, Oren, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Oren Pleniceanu,

Background

Renal cell carcinoma (RCC) is the most common tumor in the kidney and currently lacks effective treatments. Remarkably, although RCC is an extremely angiogenic tumor, existing drugs aimed at inhibiting angiogenesis have shown disappointing results in patients. One potential reason for this discrepancy is the fact that most models used to dissect the molecular mechanisms of RCC angiogenesis involve transplantation of human tumor cells into mice, which results in development of host-derived vasculature, putting into question their clinical relevance. We have previously shown that combined transplantation of human kidney cells alongside human vessel forming cells into immunodeficient mice allows the generation of vascularized reno-vascular units. Herein, we aimed to develop a novel in-vivo model that will include RCC cells and vessels that are both human-derived.

Methods

We inoculated immunodefficient NOD-SCID mice with a combination of 10⁶ fresh RCC cells and two types of human cells: (1) 5X10⁵ Endothelial Colony Forming Cells (ECFC); (2) 5X10⁵ Multipotent Stromal Cells (MSC), and analyzed the grafts following 3 weeks using immunostaining.

Results

Remarkably, the grafts developed into vascularized tumor units consisting of both RCC-like tissue, expressing classical markers of the tumor (e.g., PAX2 and PAX8), as well as human, HLA-positive blood vessels, contatining CD31+ endothelium, which were seen to feed the tumor tissue.

Conclusion

Taken together, this model represents a new purely-human inv-vivo model that allows studying the process of RCC angiogenesis, which could facilitate the uncovering of new mechanisms governing this critical process.

Funding

• Private Foundation Support