title: M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma.
abstract: Effects of M2 tumour-associated macrophages on the pathogenesis of diffuse large B cell lymphoma (DLBCL) are still controversial. Our data showed that the number of CD163-positive M2 macrophages correlated negatively with DLBCL prognosis. Macrophage depletion by clodronate liposomes significantly suppressed tumour growth in a xenograft mouse model of DLBCL using OCI-Ly3 cells. Moreover, M2 polarization of macrophages induced legumain expression in U937 cells. Exogenous legumain promoted degradation of fibronectin and collagen I, which was abolished by administration of a legumain inhibitor RR-11a. Overexpression of legumain in Raw 264.7 cells also induced tube formation of endothelial cells in matrigel. In the xenograft mouse model of DLBCL, decreased fibronectin and collagen I, as well as increased legumain expression and angiogenesis were found at the late stage tumours compared with early stage tumours. Co-localization of legumain and fibronectin was observed in the extracellular matrix of tumour tissues. Administration of the legumain inhibitor to the xenograft DLBCL model suppressed tumour growth, angiogenesis and collagen deposition compared with the control. Taken together, our results suggest that M2 tumour-associated macrophages affect degradation of the extracellular matrix and angiogenesis via overexpression of legumain, and therefore play an active role in the progression of DLBCL.
authors.affiliation: Department of Pathology Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Long
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Immunology, Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Honghao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Pathology Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Dekun
authors.initials: D
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Modern Drug Delivery and High Efficiency in Tianjin University, 92 Weijin Road, Tianjin 300072, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Pathology Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xun
authors.affiliation: Department of Pathology Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Sifan
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Immunology, Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: Department of Pathology Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Tan
mesh_terms: D000818:Animals; D015415:Biomarkers; D024042:Collagen Type I / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D005109:Extracellular Matrix / Q000276:immunology* / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D016130:Immunophenotyping; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D000099240:Asparaginyl Endopeptidase
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D003546:Cysteine Endopeptidases; D005353:Fibronectins; D000099240:Asparaginyl Endopeptidase