The tumorigenic and angiogenic effects of MGSA/GRO proteins in melanoma
The tumorigenic and angiogenic effects of MGSA/GRO proteins in melanoma
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DOI：
10.1002/jlb.67.1.53
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发表时间：
2000-01-01
影响因子：
5.5
通讯作者：
Richmond, A
中科院分区：
文献类型：
--
作者：
Haghnegahdar, H;Du, JG;Richmond, A
MGSA/GRO α、β或γ趋化因子的连续表达赋予永生化鼠黑素细胞系melan-a肿瘤形成能力。这种转化的机制尚不清楚，尽管自分泌和旁分泌过程都是可能的，因为melan-a细胞以及内皮细胞表达低水平的该配体的受体。为了进一步确定MGSA/GRO蛋白在黑素细胞转化中的作用，设计了两种类型的实验来中和MGSA/GRO在转染的melan-a克隆中的生物学作用：（1）评估MGSA/GRO蛋白的中和抗血清对melan-a肿瘤生长的作用;（2）将表达ELR基序突变形式的MGSA/GRO（具有受损的受体亲和力）的melan-a克隆的肿瘤形成能力与表达野生型MGSA/GRO的克隆的肿瘤形成能力进行比较。这些实验揭示，用表达MGSA/GRO α或γ的melan-a细胞接种并随后用相应趋化因子的抗血清处理的SCID小鼠表现出降低的肿瘤生长。这种肿瘤生长的减少伴随着MGSA/GRO γ表达肿瘤中血管生成活性的下降。此外，与用表达野生型MGSA/GRO的melan-a克隆注射的那些小鼠相比，用表达MGSA/GRO α的ELR突变形式的melan-a细胞注射的无胸腺裸鼠表现出显著受损的肿瘤形成能力。这些数据表明，MGSA/GRO蛋白的连续表达可通过刺激微血管生长进入肿瘤（旁分泌）和通过影响黑素细胞生长（自分泌）来促进肿瘤生长。
Continuous expression of the MGSA/GRO alpha, beta, or gamma chemokine bestows tumor-forming capacity to the immortalized murine melanocyte cell line, melan-a, The mechanism for this transformation is unclear, although both autocrine and paracrine processes are possible because melan-a cells as well as endothelial cells express a low level of the receptor for this ligand, To further define the role of MGSA/GRO proteins in melanocyte transformation, two types of experiments were designed to neutralize the biological effects of MGSA/GRO in the transfected melan-a clones: (1) the effect of neutralizing antiserum to MGSA/GRO proteins on melan-a tumor growth was assessed; (2) the tumor-forming capacity of melan-a clones expressing ELR motif-mutated forms of MGSA/GRO with compromised receptor affinity was compared to the tumor-forming capacity of clones expressing wild-type MGSA/GRO, These experiments revealed that SCID mice inoculated with MGSA/GRO alpha- or gamma-expressing melan-a cells and subsequently treated with antiserum to the respective chemokine exhibited decreased tumor growth. This reduction in tumor growth was accompanied by declining angiogenic activity in MGSA/GRO gamma-expressing tumors. Moreover, athymic nude mice injected with melan-a cells expressing ELR-mutant forms of MGSA/GRO alpha exhibited markedly impaired tumor-forming capacity compared with those mice injected with melan-a clones expressing wild-type MGSA/GRO, These data suggest that continuous expression of MGSA/GRO proteins may facilitate tumor growth by stimulating the growth of microvessels into the tumor (paracrine) and by affecting melanocyte growth (autocrine).