Souza Maria Carolina, Nunes Simone, Figuerêdo Samantha Hellen Santos, de Almeida Bruno Sousa, Santos Isac Patrick Conceição, Cassali Geovanni Dantas, Arruda Sérgio Marcos, Cardoso Thiago Marconi de Souza, Estrela-Lima Alessandra, Damasceno Karine Araújo
Laboratory of Experimental Pathology, Gonçalo Moniz Institute, Oswaldo Cruz Foundation, 121 Rua Waldemar Falcão, Salvador 40296-710, BA, Brazil.
Comparative Pathology Laboratory, Department of Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, 6627 Av. Pres. Antônio Carlos, Belo Horizonte 31270-901, MG, Brazil.
Cancers (Basel). 2024 Dec 4;16(23):4057. doi: 10.3390/cancers16234057.
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. : This study aimed to evaluate VCAN proteolysis and its association with ADAMTS enzymes involved in extracellular matrix remodeling in spontaneous canine mammary gland cancer. : 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. : 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. : 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.
本研究调查了VKINE，一种蛋白聚糖VCAN的生物活性蛋白水解片段，作为肿瘤细胞外基质（ECM）中的一种新的重要成分。尽管VKINE在某些肿瘤类型中的免疫调节潜力已得到认可，但其对ECM降解的影响和预后意义仍知之甚少。本研究旨在评估自发犬乳腺肿瘤中VCAN的蛋白水解作用及其与参与细胞外基质重塑的ADAMTS酶的关系。对不同预后的混合瘤（CMT）和癌肉瘤（CSS）原位及侵袭区域的VKINE、ADAMTS酶和胶原纤维的表达水平进行了比较分析。VKINE在CMT侵袭区域附近的基质中显著表达，而ADAMTS-15被确定为与VCAN蛋白水解相关的酶。在原位区域观察到III型胶原与VCAN表达之间呈负相关。我们的研究结果表明，VKINE和ADAMTS-15在肿瘤微环境中起关键作用，影响侵袭性和III型胶原沉积。本研究有助于更好地理解ECM中的动态变化，为诊断和治疗人类及犬类乳腺肿瘤的潜在新工具铺平道路。
