Infiltration of lung carcinomas with macrophages of the 27E10-positive phenotype

Endress, Holger; Freudenberg, Nikolaus; Fitzke, Edith; Grahmann, Paul Reinhard; Hasse, J; Dieter, Peter

doi:10.1016/s0169-5002(97)00042-1

Cited by 14 publications

(7 citation statements)

References 12 publications

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“…In order to characterize the presence of macrophage in®ltration in NSCLC tumors, we performed immunohistochemical staining of the tumors with HAM-56 monoclonal antibody. Consistent with the ®ndings of other authors [13,25], we found a signi®cant number of in®ltrating macrophages in NSCLC tumors. Macrophages were found throughout all tumors in a diuse and heterogeneous distribution ( Fig.…”

Section: Macrophages Are Present Throughout Nsclc Tumorssupporting

confidence: 93%

Macrophage infiltration in human non-small-cell lung cancer: the role of CC chemokines

Arenberg¹,

Keane²,

DiGiovine

et al. 2000

Cancer Immunology, Immunotherapy

130

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Bronchogenic carcinoma is the leading cause of malignancy-related mortality in the United States, with an overall 5-year survival rate of less than 15%. This aggressive behavior reflects, among other traits, the capacity of the tumor to evade normal host immune defenses, and to induce a pro-angiogenic environment. A central feature of any immune response toward tumors is the recruitment of specific immune cell populations. In the present study we investigated the infiltration of monocytes in human specimens of non-small-cell lung cancer (NSCLC). The presence of macrophages in NSCLC tumors was documented by immunohistochemistry. In vitro chemotaxis assays demonstrated higher monocyte chemotactic activity in NSCLC tumor homogenates than in normal lung tissue. We next investigated the expression of CC chemokines within specimens of NSCLC tumors. Levels of the CC chemokines were higher in NSCLC tumor tissue than in normal lung tissue. Immunolocalization showed that the cells associated with antigenic CC chemokines were the malignant tumor cells, as well as occasional stromal cells. Maximal inhibition of monocyte chemotaxis induced by NSCLC in vitro occurred in the presence of neutralizing antibodies to MCP-1 and MIP-1beta. On follow-up of 15 patients in whom we quantified macrophage infiltration, we found that those with recurrence of disease had higher levels of macrophage infiltration in their initial tumors. However, the functional significance of CC-chemokine-mediated macrophage infiltration into NSCLC remains to be determined.

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Section: Macrophages Are Present Throughout Nsclc Tumorssupporting

confidence: 93%

Macrophage infiltration in human non-small-cell lung cancer: the role of CC chemokines

Arenberg¹,

Keane²,

DiGiovine

et al. 2000

Cancer Immunology, Immunotherapy

130

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“…HLA-DR [15], iNOS [16], MRP 8/14 [17] and TNFβ [18] have been associated with improved survival in NSCLC in previous studies. It was suggested that TNFα expression is not associated with survival [18], but we have shown recently that its expression within the tumour islets correlates with improved survival, while its expression in the tumour stroma predicts poor survival [19].…”

Section: Introductionmentioning

confidence: 99%

The Tissue Microlocalisation and Cellular Expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 Is Correlated to Clinical Outcome in NSCLC

et al. 2011

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BackgroundWe have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM) expression of proteins associated with M1 and M2 macrophages in NSCLC.MethodsUsing immunohistochemistry, CD68+ macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14), or a non-cytotoxic M2 phenotype (CD163 and VEGF) were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES) (median 92.7 months) and 20 patients with poor survival (PS) (median 7.7 months).ResultsThe NM expression of NM-HLA-DR (p<0.001), NM-iNOS (p = 0.02) and NM-MRP 8/14 (p = 0.02) was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (p<0.001). There was more NM-CD163 expression (p = 0.04) but less NM-iNOS (p = 0.002) and MRP 8/14 (p = 0.01) expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR p<0.001), 65.0% versus 14.6% (NM-iNOS p = 0.003), and 54.3% versus 22.2% (NM-MRP 8/14 p = 0.04), as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41) and 19.4% versus 59.0% (NM-VEGF p = 0.001).ConclusionsCell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome.

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“…Endress et al investigated 35 lung carcinomas and 5 healthy lungs with the antibodies recognizing different macrophage subtypes. Compared to healthy lungs, the infiltration of MRP8/MRP14-positive macrophages was reduced in lung carcinomas while the number of MRP8/MRP14-positive cells was enhanced [17]. Stulik et al analyzed the expression pattern of MRP8 and MRP14 in 23 matched sets of colorectal carcinomas and normal colon mucosa using two-dimensional gel electrophoresis.…”

Section: Discussionmentioning

confidence: 99%

Expression of MRP14 gene is frequently down-regulated in Chinese human esophageal cancer

Wang

Cai

et al. 2004

Cell Res

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Migration inhibitory factor-related protein 14 (MRP14) is one of calcium-binding proteins, referred as S100A9. The heterodimeric molecule formed by MRP14 with its partner MRP8 (S100A8) is the major fatty acid carrier in neutrophils. The MRP8/14 complex has been also implicated in the intracellular transport of arachidonic acid and its precursors in keratinocytes. We show here the involvement of MRP14 in human esophageal cancer. In an initial study, mRNA differential display -reverse transcription polymerase chain reaction (DD-PCR) was performed with two esophageal carcinomas, one esophageal adenocarcinoma and matched normal adjacent mucosa. DD-PCR with the arbitrary primer OPA3 showed that one cDNA band was highly expressed in normal tissues, but disappeared or substantially decreased in tumor counterparts. It was later identified to be the 3'-end of migration inhibitory factor-related protein 14 (MRP14). Northern blotting, RT-PCR and Western blotting corroborated the down-regulation of MRP14 in 58/64 squamous cell carcinomas and 2/2 adenocarcinomas as compared with adjacent normal epithelia of the esophagus. MRP14 was undetectable in 3/3 esophageal-carcinoma cell lines. Immunochemistry demonstrated that expression of MRP14 was restricted to normal esophageal epithelia. No mutation was found in the genomic DNA of the MRP14 gene by PCR and directed DNA sequencing. Our finding suggested that the reduction of MRP14 expression is a frequent event in Chinese human esophageal cancer.

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Infiltration of lung carcinomas with macrophages of the 27E10-positive phenotype

Cited by 14 publications

References 12 publications

Macrophage infiltration in human non-small-cell lung cancer: the role of CC chemokines

Macrophage infiltration in human non-small-cell lung cancer: the role of CC chemokines

The Tissue Microlocalisation and Cellular Expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 Is Correlated to Clinical Outcome in NSCLC

Expression of MRP14 gene is frequently down-regulated in Chinese human esophageal cancer

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