School of Veterinary Science, Massey University, Palmerston North, 4442, New Zealand.
School of Veterinary Science, Massey University, Palmerston North, 4442, New Zealand.
Vet Immunol Immunopathol. 2020 Sep;227:110075. doi: 10.1016/j.vetimm.2020.110075. Epub 2020 Jun 13.
Chemokines are signaling proteins secreted by immune cells which regulate leukocyte trafficking. The aberrant expression of chemokines and their receptors by neoplastic cells influences the behaviour of many human cancers. This study evaluated gene-expression of the chemokines: CCL5, CXCL10, CXCL12 and the chemokine receptors: CXCR3, CXCR4, CXCR7, CCR4, CCR9 in 41 histologically-malignant, outcome-known, canine mammary tumours. These chemokines and chemokine receptors were selected as all were previously shown to influence the behaviour of human breast cancers. The expression of chemokines CCL5 and CXCL12 were significantly higher in tumours which subsequently metastasised than tumours that did not metastasise (p < 0.05). Increased expression of these chemokines was also correlated with shorter survival times of the dogs (CCL5: r = -0.40, p = 0.02, CXCL12: r = -0.40, p = 0.03) while CCL5 was independently prognostic of survival times (p = 0.026). A significantly higher proportion of tumours that subsequently metastasised expressed CXCR3 (p = 0.037), CXCR4 (p = 0.026), CXCR7 (p = 0.025) and CCR9 (p = 0.039) receptors while the survival times of the dogs with tumours that expressed CXCR4 (p = 0.045) and CCR9 (p = 0.039) receptors were significantly shorter than dogs with tumours that did not express these receptors. Chemokine and chemokine receptor gene-expression has not been previously correlated with disease outcome of canine mammary tumours. These findings indicate that altered expression of chemokines and their receptors influences the behaviour of canine mammary tumours suggesting a potential role of them as prognostic markers or therapeutic targets.
趋化因子是免疫细胞分泌的信号蛋白，可调节白细胞的迁移。肿瘤细胞中趋化因子及其受体的异常表达会影响许多人类癌症的行为。本研究评估了 41 例组织学恶性、已知结局的犬乳腺肿瘤中趋化因子：CCL5、CXCL10、CXCL12 和趋化因子受体：CXCR3、CXCR4、CXCR7、CCR4、CCR9 的基因表达。这些趋化因子和趋化因子受体被选择是因为它们之前都被证明会影响人类乳腺癌的行为。随后发生转移的肿瘤中趋化因子 CCL5 和 CXCL12 的表达明显高于未发生转移的肿瘤（p < 0.05）。这些趋化因子表达增加也与狗的存活时间较短相关（CCL5：r = -0.40，p = 0.02，CXCL12：r = -0.40，p = 0.03），而 CCL5 是独立预测存活时间的因素（p = 0.026）。随后发生转移的肿瘤中表达 CXCR3（p = 0.037）、CXCR4（p = 0.026）、CXCR7（p = 0.025）和 CCR9（p = 0.039）受体的比例明显更高，而表达 CXCR4（p = 0.045）和 CCR9（p = 0.039）受体的狗的存活时间明显短于未表达这些受体的狗。趋化因子和趋化因子受体的基因表达以前与犬乳腺肿瘤的疾病结局没有相关性。这些发现表明，趋化因子及其受体的表达改变会影响犬乳腺肿瘤的行为，表明它们可能作为预后标志物或治疗靶点。
