Open AccessJournal Article
Lysis of Tumor Cells by Natural Killer Cells in Mice Is Impeded by Platelets
TLDR
It is demonstrated for the first time that platelets directly protect tumor cells from NK lysis in vitro as well as in vivo, thereby promoting metastasis and surface shielding by platelet aggregates seems to be the main mechanism.Abstract:
Natural killer (NK) cells provide effective antitumoral activity in the blood stream of mice, leading to reduced metastasis. There are, however, tumor cells that metastasize despite the presence of an intact NK system. The capability of tumor cells to induce platelet aggregation, on the other hand, correlates with their enhanced metastatic potential. A counteractive role of platelets for the NK function in metastasis has never been conceived. Here we demonstrate for the first time that platelets directly protect tumor cells from NK lysis in vitro as well as in vivo. Using three different tumor cell lines in a mouse model of experimental metastasis, tumor seeding in the target organs was reduced when the host was platelet depleted, but only if the tumor cells were NK sensitive. Aggregation of platelets around tumor cells also inhibited in vitro NK tumorilytic activity. This protection of tumor cells by platelets was mouse strain independent and was equally observed with platelets from β2-microglobulin-deficient mice, excluding a NK inhibitory function of MHC class I on platelets. Thus, even if tumor cells are NK susceptible and cytotoxic NK cells threaten their survival in the blood, platelets are capable of protecting them from cytolysis, thereby promoting metastasis. Surface shielding by platelet aggregates seems to be the main mechanism of this protection.read more
Citations
More filters
Journal ArticleDOI
A Perspective on Cancer Cell Metastasis
TL;DR: It is suggested that metastasis can be portrayed as a two-phase process: the first phase involves the physical translocation of a cancer cell to a distant organ, whereas the second encompasses the ability of the cancer cellto develop into a metastatic lesion at that distant site.
Journal ArticleDOI
Microenvironmental regulation of metastasis
TL;DR: Experimental data demonstrating the role of the microenvironment in metastasis is described, areas for future research are identified and possible new therapeutic avenues are suggested.
Journal ArticleDOI
Metastasis: from dissemination to organ-specific colonization
TL;DR: Striking disparities in the natural progression of different cancers raise important questions about the evolution of metastatic traits, the genetic determinants of these properties and the mechanisms that lead to the selection of metastasis cells.
Journal ArticleDOI
Emerging Biological Principles of Metastasis
TL;DR: The cellular and molecular mechanisms involved in metastasis are summarized, with a focus on carcinomas where the most is known, and the general principles of metastasis that have begun to emerge are highlighted.
Journal ArticleDOI
Vascular Endothelial Growth Factor and Angiogenesis
Ann Hoeben,Bart Landuyt,Martin Highley,Hans Wildiers,Allan T. van Oosterom,Ernst A. de Bruijn +5 more
TL;DR: The role of V EGF in physiological and pathological processes is reviewed and how modulation of VEGF expression creates new therapeutic possibilities is discussed.
References
More filters
Journal ArticleDOI
β2-Microglobulin deficient mice lack CD4 − 8 + cytolytic T cells
TL;DR: For example, this article showed that mice homozygous for a beta 2-microglobulin gene disruption do not express any detectable beta 2m protein on the cell surface, yet are fertile and apparently healthy.
Journal ArticleDOI
P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities.
Alessandro Moretta,Massimo Vitale,Cristina Bottino,Anna Maria Orengo,Luigia Morelli,Raffaella Augugliaro,M Barbaresi,Ermanno Ciccone,Lorenzo Moretta +8 more
TL;DR: Support to the concept that p58 molecules represent a NK receptor delivering a negative signal was provided by experiments in which the entire anti-p58 mAbs could inhibit the lysis of unprotected Fc gamma R- target cells, thus mimicking the inhibitory effect of MHC class I molecules.
Journal ArticleDOI
Role of NK cells in tumour growth and metastasis in beige mice
TL;DR: It is reported here that a tumour line, modified to be sensitive to NK cytotoxicity by in vitro culture, demonstrated in vivo an increased growth rate, faster induction time and an increased metastatic capability in bg compared to control mice.
Journal ArticleDOI
Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck, and prostate. Final report of VA Cooperative Study #75.
Leo R. Zacharski,William G. Henderson,Frederick R. Rickles,Walter B. Forman,C. J. Cornell,A. Jackson Forcier,Richard L. Edwards,Elwood Headley,Sang‐Hee ‐H Kim,J. F. Ódonnell,J. F. Ódonnell,Robert O'Dell,Karl Tornyos,Hau C. Kwaan +13 more
TL;DR: The results suggest that warfarin, as a single anticoagulant agent, may favorably modify the course of some, but not all, types of human malignancy, among which is small cell carcinoma of the lung.
Journal ArticleDOI
Platelets and cancer metastasis: a causal relationship?
TL;DR: Several lines of evidence provide strong support for the concept that tumor cell-platelet interactions (i.e., TCIPA) significantly contribute to hematogenous metastasis.