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Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
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Human C1q Tumor Necrosis Factor 8 (CTRP8) defines a novel tryptase+ mast cell subpopulation in the prostate cancer
Sai Nivedita Krishnan1, Thatchawan Thanasupawat1, Leanne Arreza1
1Dept. of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Canada.
Abstract:
The adipokine C1q Tumor Necrosis Factor 8 (CTRP8) is the least known member of the 15 CTRP proteins and a ligand of the relaxin receptor RXFP1. We previously demonstrated the ability of the CTRP8-RXFP1 interaction to promote motility, matrix invasion, and drug resistance. The lack of specific tools to detect CTRP8 protein severely limits our knowledge on CTRP8 biological functions in normal and tumor tissues. Here, we have generated and characterized the first specific antiserum to human CTRP8 which identified CTRP8 as a novel marker of tryptase+ mast cells (MCT) in normal human tissues and in the prostate cancer (PC) microenvironment. Using human PC tissue microarrays composed of neoplastic and corresponding tumor-adjacent prostate tissues, we have identified a significantly higher number of CTRP8+ MCT in the peritumor versus intratumor compartment of PC tissues of Gleason scores 6 and 7. Higher numbers of CTRP8+ MCT correlated with the clinical parameter of biochemical recurrence. We showed that the human MC line ROSAKIT WT expressed RXFP1 transcripts and responded to CTRP8 treatment with a small but significant increase in cell proliferation. Like the cognate RXFP1 ligand RLN-2 and the small molecule RXFP1 agonist ML-290, CTRP8 reduced degranulation of ROSAKIT WT MC stimulated by the Ca2+-ionophore A14187. In conclusion, this is the first report to identify the RXFP1 agonist CTRP8 as a novel marker of MCT and autocrine/paracrine oncogenic factor within the PC microenvironment.
Insights
The adipokine CTRP8 is identified as a novel marker for mast cells in prostate cancer. This finding reveals CTRP8
Area of Science:
- Biochemistry
- Immunology
- Oncology
Background:
- The adipokine C1q Tumor Necrosis Factor 8 (CTRP8) is a poorly understood ligand for the relaxin receptor RXFP1.
- Previous research indicated CTRP8-RXFP1 interactions promote cancer cell motility, invasion, and drug resistance.
- Limited tools for CTRP8 detection hindered understanding of its biological roles in normal and tumor tissues.
Purpose of the Study:
- To generate and characterize the first specific antiserum for human CTRP8.
- To investigate CTRP8's role as a marker in normal and prostate cancer (PC) tissues.
- To explore CTRP8's function in mast cells (MCs) and its potential as an oncogenic factor.
Main Methods:
- Development and validation of a specific antiserum against human CTRP8.
- Analysis of human PC tissue microarrays to quantify CTRP8+ tryptase+ mast cells (MCT).
- Assessment of CTRP8's effect on human MC proliferation and degranulation in vitro.
Main Results:
- CTRP8 was identified as a novel marker for tryptase+ mast cells (MCT) in human tissues and the PC microenvironment.
- Significantly higher numbers of CTRP8+ MCT were found in the peritumor versus intratumor compartments of PC tissues (Gleason scores 6 and 7).
- Increased CTRP8+ MCT correlated with biochemical recurrence in PC patients. CTRP8 modulated MC proliferation and reduced degranulation.
Conclusions:
- CTRP8 serves as a novel marker for tryptase+ mast cells (MCT).
- CTRP8 is implicated as an autocrine/paracrine oncogenic factor within the prostate cancer microenvironment.
- This study provides essential tools and insights into CTRP8's function in cancer biology.
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