NK cell heparanase controls tumor invasion and immune surveillance

NK cells are highly efficient at preventing cancer metastasis but are infrequently found in the core of primary tumors. Here, have we demonstrated that freshly isolated mouse and human NK cells express low levels of the endo-β-D-glucuronidase heparanase that increase upon NK cell activation. Heparan...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	The Journal of clinical investigation Ročník 127; číslo 7; s. 2777 - 2788
Hlavní autoři:	Putz, Eva M., Mayfosh, Alyce J., Kos, Kevin, Barkauskas, Deborah S., Nakamura, Kyohei, Town, Liam, Goodall, Katharine J., Yee, Dean Y., Poon, Ivan K.H., Baschuk, Nikola, Souza-Fonseca-Guimaraes, Fernando, Hulett, Mark D., Smyth, Mark J.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States American Society for Clinical Investigation 01.07.2017
Témata:	Angiogenesis Animals Antitumor activity Biomedical research Breast cancer Cancer Cancer metastasis Carcinogens Carcinoma Cell activation Cell Line, Tumor Cytokines Cytokines - genetics Cytokines - immunology Development and progression Female Heparin Lyase - genetics Heparin Lyase - immunology Humans Immune checkpoint Immunologic Surveillance Immunosurveillance Immunotherapy Inflammation Killer cells Killer Cells, Natural - immunology Killer Cells, Natural - pathology Localization Lymphocytes Lymphoma Male Mammals Mammary gland Melanoma Metastases Metastasis Mice Mice, Knockout Natural killer cells Neoplasm Invasiveness - genetics Neoplasm Invasiveness - immunology Neoplasm Metastasis Neoplasms, Experimental - genetics Neoplasms, Experimental - immunology Neoplasms, Experimental - pathology NK Cell Lectin-Like Receptor Subfamily K - genetics NK Cell Lectin-Like Receptor Subfamily K - immunology NKG2 antigen Nuclear Matrix-Associated Proteins - genetics Nuclear Matrix-Associated Proteins - immunology Nucleocytoplasmic Transport Proteins - genetics Nucleocytoplasmic Transport Proteins - immunology Physiological aspects Prostate cancer Prostate carcinoma Proteins Rodents Studies T cell receptors Tumor cell lines Tumors
ISSN:	0021-9738, 1558-8238, 1558-8238
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	NK cells are highly efficient at preventing cancer metastasis but are infrequently found in the core of primary tumors. Here, have we demonstrated that freshly isolated mouse and human NK cells express low levels of the endo-β-D-glucuronidase heparanase that increase upon NK cell activation. Heparanase deficiency did not affect development, differentiation, or tissue localization of NK cells under steady-state conditions. However, mice lacking heparanase specifically in NK cells (Hpsefl/fl NKp46-iCre mice) were highly tumor prone when challenged with the carcinogen methylcholanthrene (MCA). Hpsefl/fl NKp46-iCre mice were also more susceptible to tumor growth than were their littermate controls when challenged with the established mouse lymphoma cell line RMA-S-RAE-1β, which overexpresses the NK cell group 2D (NKG2D) ligand RAE-1β, or when inoculated with metastatic melanoma, prostate carcinoma, or mammary carcinoma cell lines. NK cell invasion of primary tumors and recruitment to the site of metastasis were strictly dependent on the presence of heparanase. Cytokine and immune checkpoint blockade immunotherapy for metastases was compromised when NK cells lacked heparanase. Our data suggest that heparanase plays a critical role in NK cell invasion into tumors and thereby tumor progression and metastases. This should be considered when systemically treating cancer patients with heparanase inhibitors, since the potential adverse effect on NK cell infiltration might limit the antitumor activity of the inhibitors.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Correction/Retraction-3
ISSN:	0021-9738 1558-8238 1558-8238
DOI:	10.1172/JCI92958