Figure S1 from Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone

Maksimovic, Stefan; Boscolo, Nina C.; La Posta, Ludovica; Barrios, Sergio; Moussa, Mohammad Jad; Gentile, Emanuela; Pesquera, Pedro I.; Li, Wenjiao; Chen, Jianfeng; Gomez, Javier A.; Basi, Akshay; Burks, Jared K.; Alvarez-Breckenridge, Christopher; Gao, Jianjun; Campbell, Matthew T.; Dondossola, Eleonora

doi:10.1158/2767-9764.28727396

Figure S1 from Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone

https://doi.org/10.1158/2767-9764.28727396

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posted on 2025-04-03, 21:41 authored by Stefan Maksimovic, Nina C. Boscolo, Ludovica La Posta, Sergio Barrios, Mohammad Jad Moussa, Emanuela Gentile, Pedro I. Pesquera, Wenjiao Li, Jianfeng Chen, Javier A. Gomez, Akshay Basi, Jared K. Burks, Christopher Alvarez-Breckenridge, Jianjun Gao, Matthew T. Campbell, Eleonora Dondossola

<p>Blood vessel marker expression in bone marrow and tumors. A, B) Detection of bone marrow (A) and tumor (B) blood vessels by confocal acquisition; blue, DAPI; yellow, endomucin; red, laminin; green, tumor GFP; white boxes, magnifications reported on right panels; arrowhead, lack of physical overlap between markers; C) Immunofluorescence detection of blood vessels in VHL- RENCA bone tumors by confocal microscopy; blue, DAPI; yellow, endomucin; red, laminin; green, tumor GFP; D) Quantification of blood vessel area inside and outside tumor area based on laminin (red) and endomucin (yellow) signal, mean + SEM, n=3-4/group; blue, DAPI; green, GFP; arrowhead, blood vessels with only one marker expressed. Bar, 10 µm. Endo-endomucin; Lam-laminin; IN T-inside tumor; OUT T-outside tumor.</p>

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DOI - Is supplement to Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone

ARTICLE ABSTRACT

Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney neoplasm; bone metastasis (BM) develops in 35% to 40% of metastatic patients and results in substantial morbidity and mortality, as well as medical costs. A key feature of ccRCC is the loss of function of the von Hippel–Lindau protein, which enhances angiogenesis via vascular endothelial growth factor release. Consequently, antiangiogenic tyrosine kinase inhibitors (TKI) emerged as a treatment for ccRCC. However, limited data about their efficacy in BM is available, and no systematic comparisons have been performed. We developed mouse models of bone and lung ccRCC tumors and compared their anticancer efficacy, impact on mouse survival, and mechanisms of action, including effects on tumor cells and both immune and nonimmune (blood vessels and osteoclasts) bone stromal components. This approach elucidates the efficacy of TKIs in ccRCC bone tumors to support rational interrogation and development of therapies. TKIs showed different efficacy in synchronous bone and lung metastases and did not eradicate tumors as single agents but induced extensive reprogramming of the BM microenvironment. This resulted in a significant decrease in neoangiogenic blood vessels, bone remodeling, and immune cell infiltration (including CD8 T cells) with altered spatial distribution.

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Genitourinary Cancers Renal cancer Progression, Invasion & Metastasis Metastasis Small Molecule Agents Kinase inhibitors

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Figure S1 from Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone

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