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.

To investigate whether aldehyde dehydrogenase-1 (ALDH-1) in human lung cancer can be used as a sorting marker for stem cells in targeted therapies against human lung cancer. Spheres were induced by incubating cancer cells in a serum-free medium and formed with epidermal growth factor and fibroblast growth factor-10 (FGF10). Spheroid cells were combined with flow cytometry using the Aldefluor reagent to separate the SSCloALDEbr (ALDH-1-positive) cells. Cancer stem cells (CSCs) were characterized by their proliferation, colony formation, and tumorigenesis in nude mice and using phenotypic analysis. Float-growing spheres ("pulmospheres") were developed after SPC-A1 cells were cultured in a serum-free medium. The resultant sphere-forming cells included ALDH-1-positive cells as high as 15.13%. ALDH-1-positive CSCs have high proliferative ability, high cloning efficiency, and strong tumorigenicity. The rate of SSC(lo)ALDE(br) cell colony formation was 1.3-5.6%, whereas that of ALDE(-) cell colony formation was only 0-1.2% (P < 0.05). A cell count of only 1 × 10(3) SSC(lo)ALDE(br) cells was necessary to form tumors, whereas at least l × 10(5) ALDE(-) cells formed tumors. The same number of SSC(lo)ALDE(br) cells also formed larger tumors in a short latency period of tumor formation. The expression rates of CD133 in the SSC(lo)ALDE(br) and ALDE(-) cells were 16.31% (16.31 × 10(4)/10(6)) and 2.56% (2.56 × 10(4)/10(6)), respectively (P < 0.01). Moreover, the expression rates of ABCG2 in SSC(lo)ALDE(br) and ALDE(-) cells were 17.62% (17.62 × 10(4)/10(6)) and 3.45% (3.45 × 10(4)/10(6)), respectively (P < 0.01). Human lung adenocarcinoma bears CSCs, and ALDH-1 can act as a specific marker for human lung CSCs.

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Our results suggest that ACE gene A-240T polymorphism might be a genetic marker for the development of lung cancer in Chinese people.

Toll‐like receptor 4 ( TLR 4) plays an essential role in cancer progress. Here, we find that the expression of TLR 4 in relapsed human hepatocellular carcinoma ( HCC ) clinical samples is higher than that in the non‐relapsed ones, which leads us to explore the role of TLR 4 in cancer stemness. We reported that TLR 4‐ AKT signaling pathway was activated by lipopolysaccharides ( LPS ) in HCC cell lines to enhance the cancer stemness capacity, which was reflected by the increased percentage of CD 133 + CD 49f + population and side population, enhanced sphere formation, and the upregulation of stemness marker gene‐ SOX 2 . Downregulation of SOX 2 attenuated the enhanced HCC stemness induced by LPS , indicating SOX 2 as a downstream mediator of LPS ‐ TLR 4 signaling. The role of LPS ‐ TLR 4 signaling in inducing HCC stemness was further confirmed by tumor xenograft experiment in vivo. Taken together, our findings provide a novel therapeutic target to prevent the recurrence of HCC .