{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:31:16Z","timestamp":1791228676948,"version":"4.1.0"},"reference-count":36,"publisher":"American Society of Hematology","issue":"18","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma frequently involved in the lymph nodes, bone marrow, spleen, and gastrointestinal tract. We examined the role of IL-6 in MCL. Human MCL cells expressed the membrane gp130 and soluble gp80, and some of them also secreted IL-6. Neutralizing autocrine IL-6 and\/or blocking IL-6 receptors in IL-6+\/gp80+ MCL cells inhibited cell growth, enhanced the rate of spontaneous apoptosis, and increased sensitivity to chemotherapy drugs. For IL-6\u2212 or gp80low MCL cells, paracrine or exogenous IL-6 or gp80 protected the cells from stress-induced death. Knockdown of gp80 in gp80high MCL cells rendered the cells more sensitive to chemotherapy drugs, even in the presence of exogenous IL-6. In contrast, overexpression of gp80 in gp80low\/IL-6+ MCL cells protected the cells from chemotherapy drug-induced apoptosis in vitro and compromised the therapeutic effect of chemotherapy in vivo. IL-6 activated the Jak2\/STAT3 and PI3K\/Akt pathways in MCL, and the inhibition of these pathways completely or partially abrogated IL-6\u2013mediated protection of MCL cells. Hence, our study identifies IL-6 as a key cytokine for MCL growth and survival and suggests that targeting the IL-6 pathway may be a novel way to improve the efficacy of chemotherapy in MCL patients.<\/jats:p>","DOI":"10.1182\/blood-2012-04-424630","type":"journal-article","created":{"date-parts":[[2012,9,12]],"date-time":"2012-09-12T21:38:03Z","timestamp":1347485883000},"page":"3783-3792","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":105,"title":["Role of the microenvironment in mantle cell lymphoma: IL-6 is an important survival factor for the tumor cells"],"prefix":"10.1182","volume":"120","author":[{"given":"Liang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Lymphoma\/Myeloma, Division of Cancer Medicine, Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, 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