Cantile Monica, Scognamiglio Giosuè, Marra Laura, Aquino Gabriella, Botti Chiara, Falcone Maria Rosaria, Malzone Maria Gabriella, Liguori Giuseppina, Di Bonito Maurizio, Franco Renato, Ascierto Paolo Antonio, Botti Gerardo
Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", Napoli, Italy.
Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, Istituto Nazionale Tumori Fondazione "G. Pascale", Napoli, Italy.
J Cell Physiol. 2017 Dec;232(12):3422-3432. doi: 10.1002/jcp.25789. Epub 2017 Jun 5.
The molecular mechanisms responsible for the metastatic progression of melanoma have not been fully defined yet. We have recently shown that an important role in this process is certainly played by HOX genes, whose regulation is under control of particular non-coding RNAs, some of which are present within the HOX locus. HOTAIR is the most studied among them, whose aberrant expression is associated with the metastatic progression of many malignancies. The aim of this study was to verify the role played by HOTAIR in metastatic progression of melanoma and to evaluate the circulating levels of HOTAIR in the blood of patients with metastatic melanoma. A series of melanocytic lesions were selected to evaluate the potential changes in the expression of HOTAIR during the evolution of the disease through in situ and molecular approaches. None of the benign melanocytic lesions showed the presence of HOTAIR. The staining of HOTAIR resulted very weak in the primary pT1 lesions, while it was very strong in all pairs of primary tissues and corresponding metastases. Surprisingly, we found the presence of HOTAIR in some intratumoral lymphocytes, while this positivity decreased in lymphocyte component further away from the tumor. HOTAIR was also detected in the serum of selected metastatic patients. These data allowed us to speculate on the fundamental role played by HOTAIR in tumor evolution of melanoma. Its presence in intratumoral lymphocytes might suggest that its involvement in the modulation of tumor microenvironment and the detection in the serum could be used in the management of melanoma patients.
黑色素瘤转移进展的分子机制尚未完全明确。我们最近发现，HOX基因在这一过程中无疑发挥着重要作用，其调控受特定非编码RNA的控制，其中一些存在于HOX基因座内。HOTAIR是其中研究最多的，其异常表达与许多恶性肿瘤的转移进展相关。本研究的目的是验证HOTAIR在黑色素瘤转移进展中的作用，并评估转移性黑色素瘤患者血液中HOTAIR的循环水平。通过原位和分子方法，选择了一系列黑素细胞病变来评估疾病进展过程中HOTAIR表达的潜在变化。所有良性黑素细胞病变均未检测到HOTAIR。HOTAIR染色在原发性pT1病变中非常弱，而在所有原发性组织及其相应转移灶中都非常强。令人惊讶的是，我们在一些肿瘤内淋巴细胞中发现了HOTAIR，而在远离肿瘤的淋巴细胞成分中这种阳性率降低。在选定的转移性患者血清中也检测到了HOTAIR。这些数据使我们能够推测HOTAIR在黑色素瘤肿瘤进展中所起的重要作用。它在肿瘤内淋巴细胞中的存在可能表明其参与了肿瘤微环境的调节，而在血清中的检测可用于黑色素瘤患者的管理。
