Background:The present study investigates VKINE, a bioactive proteolytic fragment of the proteoglycan VCAN, as a novel and significant element in the tumor extracellular matrix (ECM). Although VKINE has been recognized for its immunomodulatory potential in certain tumor types, its impact on ECM degradation and prognostic implications remains poorly understood.Objectives: This study aimed to evaluate VCAN proteolysis and its association with ADAMTS enzymes involved in extracellular matrix remodeling in spontaneous canine mammary gland cancer.Methods: The expression levels of VKINE, ADAMTS enzymes, and collagen fibers were comparatively analyzed in situ and in invasive areas of carcinoma in mixed tumor (CMT) and carcinosarcoma (CSS) with different prognoses.Results: VKINE was notably expressed in the stroma adjacent to the invasion areas in CMT, whereas ADAMTS-15 was identified as the enzyme associated with VCAN proteolysis. Inverse correlations were observed between type III collagen and VCAN expression in in situ areas.Conclusions: Our findings suggest that VKINE and ADAMTS-15 play crucial roles in the tumor microenvironment, influencing invasiveness and type III collagen deposition. This study contributes to a better understanding of the dynamics within the ECM, paving the way for potential new tools in diagnosing and treating human and canine mammary tumors.
背景：本研究探讨了蛋白聚糖VCAN的生物活性蛋白水解片段VKINE，将其视为肿瘤细胞外基质（ECM）中一种新颖且重要的成分。尽管VKINE在某些肿瘤类型中已被确认具有免疫调节潜力，但其对ECM降解的影响及预后意义仍不明确。 目的：本研究旨在评估自发性犬乳腺肿瘤中VCAN蛋白水解过程及其与参与细胞外基质重塑的ADAMTS酶之间的关联。 方法：在不同预后的混合性肿瘤（CMT）和癌肉瘤（CSS）中，对原位区域和侵袭区域的VKINE、ADAMTS酶及胶原纤维表达水平进行了原位比较分析。 结果：在CMT的侵袭邻近基质中观察到VKINE显著表达，而ADAMTS-15被确认为与VCAN蛋白水解相关的关键酶。在原位区域中，III型胶原与VCAN表达呈负相关。 结论：我们的研究结果表明，VKINE和ADAMTS-15在肿瘤微环境中发挥关键作用，影响肿瘤侵袭性和III型胶原沉积。这项研究有助于深化对ECM内动态过程的理解，为开发诊断和治疗人类及犬乳腺肿瘤的新工具提供了潜在路径。
肿瘤(癌症)患者之家