Melanoma progression is a multistep evolution from a common melanocytic nevus through a radial superficial growth phase, the invasive vertical growth phase finally leading to metastatic dissemination into distant organs. Melanoma aggressiveness largely depends on the propensity to metastasize, which means the capacity to escape from the physiological microenvironment since tissue damage due to primary melanoma lesions is generally modest. Physiologically, epidermal melanocytes are attached to the basement membrane, and their adhesion/migration is under the control of surrounding keratinocytes. Thus, the epidermal compartment represents the first microenvironment responsible for melanoma spread. This complex process involves cell–cell contact and a broad range of secreted bioactive molecules. Invasion, or at the beginning of the microinvasion, implies the breakdown of the dermo-epidermal basement membrane followed by the migration of neoplastic melanocytic cells in the superficial papillary dermis. Correspondingly, several experimental evidences documented the structural and functional rearrangement of the entire tissue surrounding neoplasm that in some way reflects the atypia of tumor cells. Lastly, the microenvironment must support the proliferation and survival of melanocytes outside the normal epidermal–melanin units. This task presumably is mostly delegated to fibroblasts and ultimately to the self-autonomous capacity of melanoma cells. This review will discuss remodeling that occurs in the epidermis during melanoma formation as well as skin changes that occur independently of melanocytic hyperproliferation having possible pro-tumoral features.
黑色素瘤的进展是一个多阶段演变过程，从常见的黑色素细胞痣开始，经历放射状浅表生长期、侵袭性垂直生长期，最终导致远处器官的转移扩散。黑色素瘤的侵袭性很大程度上取决于其转移倾向，即逃离生理微环境的能力，因为原发性黑色素瘤病变造成的组织损伤通常较为有限。在生理状态下，表皮黑色素细胞附着于基底膜，其粘附/迁移受周围角质形成细胞调控。因此，表皮微环境是影响黑色素瘤扩散的首要因素。这一复杂过程涉及细胞间接触及多种分泌性生物活性分子。侵袭阶段（或微侵袭初期）意味着真皮-表皮基底膜的破坏，随后肿瘤性黑色素细胞迁移至浅层真皮乳头层。相应的实验证据表明，肿瘤周围整体组织会发生结构和功能的重排，这在某种程度上反映了肿瘤细胞的异型性。最后，微环境必须支持黑色素细胞在正常表皮-黑色素单元外的增殖与存活。这一任务可能主要依赖于成纤维细胞，并最终取决于黑色素瘤细胞的自主能力。本综述将探讨黑色素瘤形成过程中表皮发生的重塑现象，以及独立于黑色素细胞过度增殖、可能具有促肿瘤特征的皮肤变化。
The Keratinocyte in the Picture Cutaneous Melanoma Microenvironment
肿瘤(癌症)患者之家