Lozupone F, Fais S
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità (National Institute of Health), Viale Regina Elena, 299, 00161 - Rome, Italy.
Curr Mol Med. 2015;15(9):836-41. doi: 10.2174/1566524015666151026100916.
Cancer cell cannibalism is currently defined as a phenomenon in which an ensemble of a larger cell containing a smaller one, often in a big cytoplasmic vacuole, is detected in either cultured tumor cells or a tumor sample. After almost one century of considering this phenomenon as a sort of neglected curiosity, some recent studies have first proposed tumor cell cannibalism as a sort of "aberrant phagocytosis", making malignant cells very similar to professional phagocytes. Later, further research has shown that, differently to macrophages, exclusively ingesting exogenous material, apoptotic bodies, or cell debris, tumor cells are able to engulf other cells, including lymphocytes and erythrocytes, either dead or alive, with the main purpose to feed on them. This phenomenon has been associated to the malignancy of tumors, mostly exclusive of metastatic cells, and often associated to poor prognosis. The cannibalistic behavior increased depending on the microenvironmental condition of tumor cells, such as low nutrient supply or low pH, suggesting its key survival option for malignant cancers. However, the evidence that malignant cells may cannibalize tumor-infiltrating lymphocytes that act as their killers, suggests that tumor cell cannibalism could be a very direct and efficient way to neutralize immune response, as well. Tumor cell cannibalism may represent a sign of regression to a simpler, ancestral or primeval life style, similar to that of unicellular microorganisms, such as amoebas, where the goal is to survive and propagate in an overcrowded and very hostile microenvironment. In fact, we discovered that metastatic melanoma cells share with amoebas a transmembrane protein TM9SF4, indeed related to the cannibal behavior of these cells. This review attempts to provide a comprehensive description of the current knowledge about the role of TM9SF4 in cancer, highlighting its role as a key player in the cannibal behavior of malignant cancer cells. Moreover, we discuss differences and similarities between tumor cannibalism, entosis, phagocytosis and emperipolesis.
癌细胞吞噬作用目前被定义为一种现象，即在培养的肿瘤细胞或肿瘤样本中检测到一个包含较小细胞的较大细胞集合体，较小细胞通常存在于一个大的细胞质液泡中。在将这种现象视为一种被忽视的奇闻轶事近一个世纪之后，最近的一些研究首次提出肿瘤细胞吞噬作用是一种“异常吞噬作用”，使得恶性细胞与专业吞噬细胞非常相似。后来，进一步的研究表明，与巨噬细胞不同，巨噬细胞仅摄取外源性物质、凋亡小体或细胞碎片，而肿瘤细胞能够吞噬其他细胞，包括死的或活的淋巴细胞和红细胞，其主要目的是以它们为食。这种现象与肿瘤的恶性程度相关，主要不包括转移细胞，并且常常与预后不良相关。吞噬行为会根据肿瘤细胞的微环境条件而增加，例如低营养供应或低pH值，这表明它是恶性肿瘤关键的生存选择。然而，恶性细胞可能吞噬作为其杀手的肿瘤浸润淋巴细胞这一证据表明，肿瘤细胞吞噬作用也可能是一种非常直接且有效的中和免疫反应的方式。肿瘤细胞吞噬作用可能代表着向一种更简单、原始或远古生活方式的回归，类似于单细胞微生物，如变形虫，其目标是在过度拥挤且非常恶劣的微环境中生存和繁殖。事实上，我们发现转移性黑色素瘤细胞与变形虫共享一种跨膜蛋白TM9SF4，它确实与这些细胞的吞噬行为有关。这篇综述试图全面描述目前关于TM9SF4在癌症中的作用的知识，强调其作为恶性癌细胞吞噬行为关键参与者的作用。此外，我们还讨论了肿瘤吞噬作用、细胞内吞、吞噬作用和血细胞渗出之间的异同。
