Literature Analysis: Bidirectional Crosstalk Between Clear Cell Renal Cell Carcinoma (ccRCC) and Perirenal Adipose Tissue, Empowered by ANT BIO's Multiplex Fluorescence IHC Solutions

1. Literature Information

Journal: Cell Metabolism

Impact Factor: 27.287

Key Products Utilized: 5-Color Multiplex Fluorescence IHC Staining Kit (Catalog No.: abs50013) and a series of antibody products (Anti-CD36: abs120668; Anti-PTHR: abs135215; Anti-CT: abs120479; Anti-MCT4: abs124388) from the Absin product line of ANT BIO PTE. LTD.

2. Research Background

Clear Cell Renal Cell Carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma, characterized by unique metabolic reprogramming and close interactions with the surrounding tumor microenvironment (TME). Perirenal Adipose Tissue (PAT), as a key component of the ccRCC TME, has been increasingly recognized as a critical regulator of tumor progression. However, the underlying mechanisms of crosstalk between ccRCC cells and PAT remain incompletely understood, particularly regarding the role of adipose tissue browning in tumor development.

Tyrosine Kinase Inhibitors (TKIs) are widely used as first-line therapeutic agents for advanced ccRCC. Nevertheless, clinical observations have shown that TKI efficacy varies among patients, and the reasons for reduced therapeutic effects in certain cases are not fully elucidated. Exploring the potential crosstalk between ccRCC and PAT, as well as the impact of TKIs on this interaction, may provide new insights into optimizing ccRCC treatment strategies.

3. Research Approach

The research team initiated the study by examining perirenal white adipose tissue (WAT) samples adjacent to human ccRCC tissues, aiming to investigate morphological and functional changes in adipose tissue within the tumor microenvironment. They first observed obvious browning signs in these WAT samples, prompting further exploration of the bidirectional communication between ccRCC and PAT.

To characterize the role of beige adipocytes (brown-like adipocytes derived from WAT) in ccRCC progression, the team employed multiplex fluorescence immunohistochemistry (mIHC) technology using ANT BIO PTE. LTD.'s products to detect key markers of beige adipocytes and related functional molecules in tissue samples. Subsequently, they constructed in vitro co-culture systems of ccRCC cells and perirenal adipocytes to verify the bidirectional regulatory effects between the two cell types. To explore the molecular mechanisms underlying the crosstalk, the research team analyzed the changes in cytokine secretion profiles and signaling pathway activation in both cell types during co-culture. Finally, in vivo animal models and clinical sample analyses were conducted to validate the findings from in vitro experiments and investigate the correlation between adipose tissue browning and TKI therapeutic efficacy in ccRCC patients.

4. Research Results

First, the research team confirmed that perirenal WAT adjacent to ccRCC tissues undergoes significant browning, with increased expression of beige adipocyte markers (such as UCP1 and PGC1α) detected by mIHC using ANT BIO PTE. LTD.'s 5-Color Multiplex Fluorescence IHC Staining Kit (abs50013) and specific antibodies. This browning phenomenon was not observed in perirenal WAT from non-tumor patients, indicating a tumor-specific induction effect.

In vitro co-culture experiments revealed bidirectional crosstalk between ccRCC cells and perirenal adipocytes: ccRCC cells secreted factors that promoted adipocyte browning, while beige adipocytes enhanced ccRCC cell proliferation, migration, and invasion. Mechanistically, the team identified that ccRCC cells upregulated adipocyte browning through the secretion of parathyroid hormone-related protein (PTHrP), which activated the PTHR signaling pathway in adipocytes. Conversely, beige adipocytes released lactate via MCT4 (detected by Anti-MCT4 antibody, abs124388), which was taken up by ccRCC cells through CD36 (detected by Anti-CD36 antibody, abs120668) to fuel tumor metabolism and progression.

Clinical sample analysis and in vivo experiments further demonstrated that adipose tissue browning was positively correlated with advanced tumor stage and poor prognosis in ccRCC patients. Moreover, TKIs treatment was found to inhibit adipocyte browning by downregulating PTHrP secretion from ccRCC cells, thereby weakening the pro-tumor effect of beige adipocytes. Patients with higher levels of adipose tissue browning showed better responses to TKI therapy, suggesting that adipose tissue browning could serve as a potential predictive biomarker for TKI efficacy.

5. Product Empowerment

ANT BIO PTE. LTD.'s products played a pivotal role in validating the key findings of this research. The 5-Color Multiplex Fluorescence IHC Staining Kit (abs50013) from the Absin product line enabled simultaneous detection of multiple target molecules (e.g., UCP1, PGC1α, CD36, MCT4) in a single tissue section, facilitating the accurate characterization of adipose tissue browning and the spatial distribution of functional molecules at the tumor-adipose tissue interface. This multiplex detection capability eliminated the limitations of traditional single-staining techniques, significantly improving the efficiency and comprehensiveness of tissue analysis.

Additionally, the series of high-specificity antibody products (Anti-CD36: abs120668; Anti-PTHR: abs135215; Anti-CT: abs120479; Anti-MCT4: abs124388) provided by ANT BIO PTE. LTD. ensured the reliability and accuracy of target protein detection. The high affinity and low non-specific binding of these antibodies allowed for precise quantification of protein expression levels, which was critical for confirming the correlation between adipose tissue browning and ccRCC progression, as well as elucidating the underlying molecular mechanisms of bidirectional crosstalk.

6. Brand Mission

ANT BIO PTE. LTD. is dedicated to empowering life science research through the provision of high-quality, reliable reagents and comprehensive solutions. Our specialized sub-brands (Absin, Starter, UA) are strategically positioned to cover a full spectrum of research needs: Absin focuses on general reagents and kits, Starter specializes in antibodies, and UA is dedicated to recombinant proteins. We strive to support researchers in unlocking scientific mysteries, advancing medical progress, and addressing unmet clinical needs through continuous innovation and customer-centric services.

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8. Disclaimer

This article is AI-compiled and interpreted based on the original work in DOI: 10.1002/advs.202413562. All intellectual property (e.g., images, data) of the original publication shall belong to the journal and the research team. For any infringement, please contact us promptly and we will take immediate action.

9. Brand Promotion Copy

ANT BIO PTE. LTD. – Empowering Scientific Breakthroughs

At ANTBIO, we are committed to advancing life science research through high-quality, reliable reagents and comprehensive solutions. Our specialized sub-brands (Absin, Starter, UA) cover a full spectrum of research needs, from general reagents and kits to antibodies and recombinant proteins. With a focus on innovation, quality, and customer-centricity, we strive to be your trusted partner in unlocking scientific mysteries and driving medical progress. Explore our product portfolio today and elevate your research to new heights.