Significance of Macrophage Chemoattractant Protein-1 Expression and Macrophage Infiltration in Squamous Cell Carcinoma of the Esophagusa

Koide, Naoki; Nishio, Akira; Sato, Toshiyuki; Sugiyama, Atsushi; Miyagawa, Shinichi

doi:10.1111/j.1572-0241.2004.30733.x

Cited by 151 publications

(123 citation statements)

References 18 publications

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“…38 Tumour infiltrating macrophages as such can act as promoters of tumour progression, 39 and it has been reported that macrophages in SCCs of oesophagus contribute to a poor prognosis through the secretion of Macrophage Chemoattractant Protein-1. 40 In contrast; the degree of macrophage infiltration was a favourable prognostic sign in lower gastric cancer. 41 Our data do, however, indicate that a high uPARscore in macrophages at the invasive front leads to shorter survival in adenocarcinomas in and near to the lower oesophagus (see Fig.…”

Section: Discussionmentioning

confidence: 94%

Prognosis in adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia evaluated by uPAR‐immunohistochemistry

Lærum

Øvrebø

Skarstein

et al. 2011

Intl Journal of Cancer

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Adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia in humans are highly invasive tumours with poor prognosis. The localisation of urokinase‐type plasminogen activator receptor (uPAR) was determined in 66 patients; 60 with adenocarcinomas and six cases with Barrett's oesophagus. uPAR was expressed in nearly all cases of invasive adenocarcinomas by populations of cancer cells, macrophages and myofibroblasts at both the invasion front and the tumour core. In areas with high‐grade dysplasia or with Barrett's metaplasia adjacent to the tumour tissue, no uPAR‐immunoreactivity was found. High local expression of uPAR, therefore, appears to be a characteristic marker for invasive behaviour in this tumour, suggesting that uPAR's contribution to matrix degradation during invasive growth is a late event in carcinogenesis. Using a scoring system for semiquantitative estimation of uPAR‐positivity on immmunohistochemically stained specimens, a significant association was found between poor overall survival and high uPAR‐score for cancer cells in the tumour core and for macrophages peripherally at the tumour invasion zone. In multivariate analysis, these two uPAR‐scores were confirmed as highly significant prognostic parameters independent of Tumour, Node, Metastasis (TNM)‐stage and World Health Organization (WHO) classification. The proteolytic action of these malignant and nonmalignant accessory cells thus seemed to follow two main patterns: one dominated by uPAR positive cancer cells and one by uPAR‐positive macrophages. Scoring of uPAR‐positivity might be a useful parameter for onset of invasion and prognosis in these adenocarcinomas.

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Section: Discussionmentioning

confidence: 94%

Prognosis in adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia evaluated by uPAR‐immunohistochemistry

Lærum

Øvrebø

Skarstein

et al. 2011

Intl Journal of Cancer

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“…Furthermore, our data are in agreement with data reporting MCP-1 expression in a variety of human tumour cell lines including gastric, 10 ovarian, 45 breast, 9 melanoma, 46 pancreatic 7 and neuroblastoma cancer cell lines. 47 Similarly, in vivo, MCP-1 was expressed by tumour cells of different types including ovarian, 45,48 gastric, 10 pancreatic, 7 oesophageal 16,18 and also breast carcinoma cells. 8,9,17 More particularly in accordance with our results showing a selective expression of MCP-1 in invasive breast tumour cell lines, Valkovic et al 17 have shown that MCP-1 overexpression in tumour breast carcinoma 52,53 prostate cancer cells 54 and bladder cancer cells.…”

Section: Discussionmentioning

confidence: 95%

“…The correlation between MCP-1 expression and a poor prognosis was also demonstrated for the squamous cell carcinoma of the oesophagus. 16 In tumours, MCP-1 is produced both by peritumoral stromal cells and by tumour cells themselves, but an overexpression of MCP-1 in invasive tumour cells has been documented in several human carcinomas including breast, gastric and oesophageal carcinomas. 10,17,18 If the functional implication of MCP-1 in tumour progression is therefore largely documented, the mechanisms regulating MCP-1 expression in tumour cells are still poorly understood.…”

mentioning

confidence: 99%

Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

Mestdagt

Polette

Butticè

et al. 2005

Intl Journal of Cancer

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The loss of E-cadherin expression and the translocation of b-catenin to the nucleus are frequently associated with the metastatic conversion of epithelial cells. In the nucleus, b-catenin binds to the TCF/LEF-1 (T-cell factor/ lymphoid enhancer factor) transcription factor family resulting in the activation of several genes, some of them having important implications in tumour progression. In our study, we investigated the potential regulation of monocyte chemotactic protein-1 (MCP-1/CCL2) expression by the b-catenin/TCF pathway. This CC-chemokine has been implicated in tumour progression events such as angiogenesis or tumour associated macrophage (TAM) infiltration. We thus demonstrated that MCP-1 expression correlates with the reorganization of the E-cadherin/b-catenin complexes. Indeed, MCP-1 was expressed by invasive breast cancer cells (MDA-MB-231, BT549 and Hs578T), which do not express E-cadherin but was not produced by noninvasive breast cancer cell lines (MCF7 and T47D) expressing high level of E-cadherin. In addition, the MCP-1 promoter was activated in BT549 breast cancer cells transfected with b-catenin and TCF-4 cDNAs. The MCP-1 mRNA level was similarly upregulated. Moreover, we showed that MCP-1 mRNA was downregulated after transfection with a siRNA against b-catenin in both BT549 and Hs578T cells. Our results therefore identify MCP-1 as a target of the b-catenin/TCF/LEF pathway in breast tumour cells, a regulation which could play a key role in breast tumour progression. ' 2005 Wiley-Liss, Inc.Key words: MCP-1; b-catenin; breast cancer Chemokines constitute a superfamily of proinflammatory cytokines that are implicated in tumour progression, modulating not only host tumour-specific immunological response but also angiogenesis or tumour cell invasion and proliferation. 1-3 Monocyte chemotactic protein-1 (MCP-1) or CCL2 is a CC-chemokine that specifically attracts monocytes and memory T cells. It has been particularly implicated in processes characterized by mononuclear cell infiltration including breast cancer. 4,5 In some models, MCP-1 has been shown to display an antitumoral effect. 6,7 Nevertheless, a large number of studies demonstrate that MCP-1 facilitates tumour progression through its ability to recruit stromal cells including tumour associated macrophages (TAMs) and endothelial cells. 7-10 A pro-angiogenic role of MCP-1 has been demonstrated in many systems, facilitating tumour growth and dissemination. 8,9,11,12 Moreover, a direct effect of MCP-1 on tumour cell migration in vitro has also been described. 13 Recently, Lebrecht et al. 14 have correlated an increased MCP-1 serum level with an advanced breast tumour stage and the presence of lymph node metastasis. In the same way, Amann et al. 15 reported a significant association between MCP-1 urinary levels and tumour stage and grade. They suggested a use of its urinary level as prognosis marker in bladder cancer. The correlation between MCP-1 expression and a poor prognosis was also demonstrated for the squamous cell carcinoma of the oeso...

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“…Similarly, increasing tumour-infiltrating lymphocyte count has been linked with decreased risk of death from gastric cancer in one study, but associated with an adverse prognosis in another (Setala et al, 1996;Grogg et al, 2003). Studies relating to oesophageal cancer are equally contradictory (Ma et al, 1999;Koide et al, 2004). In this study, there were no differences in tissue cytokine concentrations (mRNA or protein) between tumours with a chronic inflammatory infiltrate and those without, suggesting that differential tissue IL-1b expression is likely to be tumour-cell derived.…”

Section: Discussionmentioning

confidence: 99%

Elevated tumour interleukin-1β is associated with systemic inflammation: a marker of reduced survival in gastro-oesophageal cancer

et al. 2006

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Systemic inflammation is associated with adverse prognosis cancer but its aetiology remains unclear. We investigated the expression of proinflammatory cytokines within normal mucosa from healthy controls and tumour tissue in cancer patients and related these levels with markers of systemic inflammation and with the presence of a tumour inflammatory infiltrate. Tissue was collected from 56 patients with gastro-oesophageal cancer and from 12 healthy controls. Tissue cytokine mRNA concentrations were measured by real-time PCR and tissue protein concentrations by cytometric bead array. The degree of chronic inflammatory cell infiltrate was recorded. Serum cytokine and acute phase protein concentrations (including C-reactive protein (CRP)) were measured by enzymelinked immunosorbent assay. Proinflammatory cytokines were significantly overexpressed (interleukin (IL)-1b, IL-6, IL-8 and tumour necrosis factor-a) both at mRNA and protein levels in the cancer specimens compared with mucosa from controls. Interleukin-1b was expressed in greatest (10 -100-fold) concentration and protein levels correlated significantly with systemic inflammation (CRP) (P ¼ 0.05, r ¼ 0.31). A chronic inflammatory infiltrate was observed in 75% of the cancer specimens and was associated with systemic inflammation (CRP: P ¼ 0.01). However, the presence of chronic inflammation per se was not associated with altered cytokine expression within the tumour. Both a chronic inflammatory infiltrate and systemic inflammation (CRP) were associated with reduced survival (P ¼ 0.05 and P ¼ 0.03, respectively). Tumour chronic inflammatory infiltrate and tumour tissue IL-1b overexpression are potential independent factors influencing systemic inflammation in oesophagogastric cancer patients.

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Significance of Macrophage Chemoattractant Protein-1 Expression and Macrophage Infiltration in Squamous Cell Carcinoma of the Esophagusa

Cited by 151 publications

References 18 publications

Prognosis in adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia evaluated by uPAR‐immunohistochemistry

Prognosis in adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia evaluated by uPAR‐immunohistochemistry

Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

Elevated tumour interleukin-1β is associated with systemic inflammation: a marker of reduced survival in gastro-oesophageal cancer

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