Moretti S, Pinzi C, Spallanzani A, Berti E, Chiarugi A, Mazzoli S, Fabiani M, Vallecchi C, Herlyn M
Second Dermatology Unit, S. Maria Nuova Hospital, Azienda Sanitaria di Firenze, Florence, Italy.
Int J Cancer. 1999 Apr 20;84(2):160-8. doi: 10.1002/(sici)1097-0215(19990420)84:2<160::aid-ijc12>3.0.co;2-r.
Melanoma cells in culture express a variety of growth factors and cytokines and some of their autocrine and paracrine roles have been investigated. However, less information is available on the potential dynamic changes in expression of these molecules on cells during melanoma development and progression in situ. Using immunohistochemistry, we tested 40 nevi and primary and metastatic melanoma lesions for the expression of 10 growth factors and cytokines and the respective receptors representing 10 cell surface molecules. Nevi and thin (< 1 mm) primary melanomas showed little expression of ligands except weak reactivity of tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), interleukin-8 (IL-8) and reactivity of TGF-betaR and c-kit. Marked up-regulation of growth factors, cytokines and receptor expression was observed in thick (> 1 mm) primary melanomas, which were stained with polyclonal or monoclonal antibodies (MAbs) for IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha, TGF-beta, granulocyte-macrophage colony-stimulating factor (GMCSF) and stem cell factor (SCF), but not IL-2. Metastases showed similar expression patterns except that SCF was absent. Co-expression of ligand and receptor was observed for TGF-beta, GM-CSF and IL-6, suggesting an autocrine role for these ligands. TNF-alpha appears to be a marker of benign lesions; IL-6 and IL-8 expression is associated with biologically early malignancy; TGF-beta, GM-CSF and IL-1alpha are highly expressed in biologically late lesions; and TNF-beta is an apparent marker of metastatic dissemination. Our results indicate that melanoma cells utilize cascades of growth factors and cytokines for their progression.
培养的黑色素瘤细胞表达多种生长因子和细胞因子，并且对其中一些因子的自分泌和旁分泌作用进行了研究。然而，关于这些分子在原位黑色素瘤发生发展过程中细胞上表达的潜在动态变化的信息较少。我们利用免疫组织化学方法，检测了40例痣、原发性和转移性黑色素瘤病变中10种生长因子、细胞因子以及代表10种细胞表面分子的相应受体的表达情况。痣和薄的（<1mm）原发性黑色素瘤除肿瘤坏死因子-α（TNF-α）、转化生长因子-β（TGF-β）、白细胞介素-8（IL-8）有弱反应性以及TGF-βR和c-kit有反应性外，配体表达很少。在厚的（>1mm）原发性黑色素瘤中观察到生长因子、细胞因子和受体表达明显上调，这些肿瘤用针对IL-1α、IL-1β、IL-6、IL-8、TNF-α、TGF-β、粒细胞-巨噬细胞集落刺激因子（GMCSF）和干细胞因子（SCF）的多克隆或单克隆抗体（MAbs）染色，但IL-2未染色。转移灶显示出相似的表达模式，只是没有SCF。观察到TGF-β、GM-CSF和IL-6的配体和受体共表达，提示这些配体具有自分泌作用。TNF-α似乎是良性病变的标志物；IL-6和IL-8的表达与生物学上早期恶性肿瘤相关；TGF-β、GM-CSF和IL-1α在生物学上晚期病变中高表达；而TNF-β是转移扩散的明显标志物。我们的结果表明，黑色素瘤细胞利用生长因子和细胞因子级联反应促进其进展。
