Abstract:
BACKGROUND:Several stromal cell subtypes including macrophages contribute to tumor progression by inducing epithelial-mesenchymal transition (EMT) at the invasive front, a mechanism also linked to metastasis. Tumor associated macrophages (TAM) reside mainly at the invasive front but they also infiltrate tumors and in this process they mainly assume a tumor promoting phenotype. In this study, we asked if TAMs also regulate EMT intratumorally. We found that TAMs through TGF-β signaling and activation of the β-catenin pathway can induce EMT in intratumoral cancer cells. METHODS:We depleted macrophages in F9-teratocarcinoma bearing mice using clodronate-liposomes and analyzed the tumors for correlations between gene and protein expression of EMT-associated and macrophage markers. The functional relationship between TAMs and EMT was characterized in vitro in the murine F9 and mammary gland NMuMG cells, using a conditioned medium culture approach. The clinical relevance of our findings was evaluated on a tissue microarray cohort representing 491 patients with non-small cell lung cancer (NSCLC). RESULTS:Gene expression analysis of F9-teratocarcinomas revealed a positive correlation between TAM-densities and mesenchymal marker expression. Moreover, immunohistochemistry showed that TAMs cluster with EMT phenotype cells in the tumors. In vitro, long term exposure of F9-and NMuMG-cells to macrophage-conditioned medium led to decreased expression of the epithelial adhesion protein E-cadherin, activation of the EMT-mediating β-catenin pathway, increased expression of mesenchymal markers and an invasive phenotype. In a candidate based screen, macrophage-derived TGF-β was identified as the main inducer of this EMT-associated phenotype. Lastly, immunohistochemical analysis of NSCLC patient samples identified a positive correlation between intratumoral macrophage densities, EMT markers, intraepithelial TGF-β levels and tumor grade. CONCLUSIONS:Data presented here identify a novel role for macrophages in EMT-promoted tumor progression. The observation that TAMs cluster with intra-epithelial fibroblastoid cells suggests that the role of macrophages in tumor-EMT extends beyond the invasive front. As macrophage infiltration and pronounced EMT tumor phenotype correlate with increased grade in NSCLC patients, we propose that TAMs also promote tumor progression by inducing EMT locally in tumors.
journal_name
BMC Cancerjournal_title
BMC cancerauthors
Bonde AK,Tischler V,Kumar S,Soltermann A,Schwendener RAdoi
10.1186/1471-2407-12-35subject
Has Abstractpub_date
2012-01-24 00:00:00pages
35issn
1471-2407pii
1471-2407-12-35journal_volume
12pub_type
杂志文章相关文献
BMC CANCER文献大全abstract:BACKGROUND:Breast cancer is the leading cause of cancer mortality among women in Malaysia. Delayed diagnosis is preventable and has major effects on patients' prognosis and survival. The objectives of our study were to identify the magnitude of delayed diagnosis and its associated factors in women with breast cancer in...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-11-141
更新日期:2011-04-17 00:00:00
abstract:BACKGROUND:Transforming growth factor (TGF)-β plays a pivotal role in cancer progression through regulating cancer cell proliferation, invasion, and remodeling of the tumor microenvironment. Cancer-associated fibroblasts (CAFs) are the predominant type of stromal cell, in which TGF-β signaling is activated. Among the s...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-14-580
更新日期:2014-08-09 00:00:00
abstract:BACKGROUND:More than 50% of metastatic melanoma patients have a specific mutation in the serine/threonine kinase BRAF. This results in constitutive activation of the RAS-RAF-MEK-ERK-MAP kinase pathway, which causes uncontrolled cell growth. Vemurafenib (PLX4032) is an oral chemotherapeutic agent that targets the specif...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-018-4583-3
更新日期:2018-06-22 00:00:00
abstract:BACKGROUND:Chromosomal and genomic aberrations are common features of human cancers. However, chromosomal numerical and structural aberrations, breakpoints and disrupted genes have yet to be identified in esophageal squamous cell carcinoma (ESCC). METHODS:Using multiplex-fluorescence in situ hybridization (M-FISH) and...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-12-367
更新日期:2012-08-24 00:00:00
abstract:BACKGROUND:Most staging systems for soft tissue sarcoma are based on histologic malignancy-grade, tumor size and tumor depth. These factors are generally dichotomized, size at 5 cm. We believe it is unlikely that tumor depth per se should influence a tumor's metastatic capability. Therefore we hypothesized that the unf...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-3-17
更新日期:2003-05-26 00:00:00
abstract:BACKGROUND:The prognostic value of p53 protein expression in esophageal cancer has been evaluated, but the results remain inconclusive and no consensus has yet been achieved. This meta-analysis was conducted to quantitatively assess the prognostic significance of p53 expression in esophageal cancer. METHODS:Publicatio...
journal_title:BMC cancer
pub_type: 杂志文章,meta分析
doi:10.1186/s12885-016-2427-6
更新日期:2016-07-01 00:00:00
abstract:BACKGROUND:Triple-negative breast cancer (TNBC) exhibit characteristics quite distinct from other kinds of breast cancer, presenting as an aggressive disease--recurring and metastasizing more often than other kinds of breast cancer, without tumor-specific treatment options and accounts for 15% of all types of breast ca...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-12-120
更新日期:2012-03-27 00:00:00
abstract:BACKGROUND:Cancer survivors and their caregivers may have various unmet needs that are medically difficult to solve. Previous studies have suggested the relations between individuals' backgrounds and their unmet needs. We conducted a large-scale analysis to clarify the influence of individuals' backgrounds, primarily c...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-06732-5
更新日期:2020-03-30 00:00:00
abstract:BACKGROUND:Interpretation of comparative health-related quality of life (HRQOL) studies following different prostate cancer treatments is often difficult due to differing patient ages. Furthermore, age-related changes can hardly be discriminated from therapy-related changes. The evaluation of age-and comorbidity-relate...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-9-296
更新日期:2009-08-24 00:00:00
abstract:BACKGROUND:CRC is one of the most common malignancies worldwide, and its molecular mechanisms remain unclear. Elevated levels of BAG3 have been reported in various tumors. The present study aimed to explore the expression and function of BAG3 in CRC. METHODS:BAG3 protein expression was evaluated in 90 CRC specimens us...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-018-4657-2
更新日期:2018-08-06 00:00:00
abstract:BACKGROUND:Primary angiosarcomas of the right atrium are extremely rare, often resulted in missed diagnosis or misdiagnosis with routine examination tools. These malignant cardiac tumors are highly aggressive with generally poor prognosis. Surgical excision is the mainstay of treatment as it is essentially not responsi...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-019-6450-2
更新日期:2020-01-06 00:00:00
abstract:BACKGROUND:Myopericytoma is a rare and usually benign tumor, which is even rarer if it occurs in the liver and stomach space. Previous reports of myopericytoma were mostly related to its pathological manifestations, while imaging reports were rare. Here, we report the computed tomography (CT), computed tomography angio...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-017-3146-3
更新日期:2017-02-20 00:00:00
abstract:BACKGROUND:Our aim was to investigate the value of serum squamous cell carcinoma (SCC) antigen levels in predicting chemosensitivity, lymph node metastasis, as well as prognosis in patients with cervical squamous cell carcinoma who received neoadjuvant chemotherapy (NACT). METHODS:This retrospective study enrolled 103...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-06934-x
更新日期:2020-05-14 00:00:00
abstract:BACKGROUND:Ethyl carbamate (EC) is a multi-site carcinogen in experimental animals and probably carcinogenic to humans (IARC group 2A). Traces of EC below health-relevant ranges naturally occur in several fermented foods and beverages, while higher concentrations above 1 mg/l are regularly detected in only certain spir...
journal_title:BMC cancer
pub_type: 杂志文章,meta分析,评审
doi:10.1186/1471-2407-10-266
更新日期:2010-06-08 00:00:00
abstract:BACKGROUND:The relationship between non-steroidal anti-inflammatory drug (NSAID) consumption and breast cancer has been repeatedly studied, although the results remain controversial. Most case-control studies reported that NSAID consumption protected against breast cancer, while most cohort studies did not find this ef...
journal_title:BMC cancer
pub_type: 杂志文章,多中心研究
doi:10.1186/s12885-016-2692-4
更新日期:2016-08-20 00:00:00
abstract:BACKGROUND:During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these int...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-9-98
更新日期:2009-03-30 00:00:00
abstract:BACKGROUND:In past decades, circular RNAs (circRNAs) have achieved increasing attention because of its regulatory role in different kinds of cancers. However, how circAGFG1 regulates cervical cancer (CC) is still largely undiscovered. This study aims to evaluate the role of a novel circRNAs and related molecular mechan...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-019-6269-x
更新日期:2019-11-08 00:00:00
abstract:BACKGROUND:From 2008, Danish general practitioners could refer patients suspected of having cancer to standardised cancer patient pathways (CPPs). We aimed to compare the length of the diagnostic interval in 2010 with the length of the diagnostic interval before (2004/05) and during (2007/08) the implementation of CPPs...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-015-1317-7
更新日期:2015-04-23 00:00:00
abstract:BACKGROUND:Methyl-CpG binding domain protein 1 (MBD1), a suppressor of gene transcription, may be involved in inactivation of tumor suppressor genes during tumorigenesis. Over-expression of MBD1 has been reported in human pancreatic carcinomas. METHODS:In this study, we established a MBD1-knock-down pancreatic cancer ...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-8-121
更新日期:2008-04-29 00:00:00
abstract:BACKGROUND:There are three main therapeutic strategies, namely expectant management (dilation and curettage only), prophylactic chemotherapy and prophylactic total hysterectomy for treating older women with complete hydatidiform mole (CHM). However, the scientific community has so far, not unanimously accepted the abov...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-017-3749-8
更新日期:2017-11-09 00:00:00
abstract:BACKGROUND:Sentinel lymph node metastasis is a common and early event in the metastatic process of head and neck squamous cell carcinoma (HNSCC) and is the most powerful prognostic factor for survival of HNSCC patients. 3-O-acetyloleanolic acid (3AOA), a pentacyclic triterpenoid compound isolated from seeds of Vigna si...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-018-4630-0
更新日期:2018-07-05 00:00:00
abstract:BACKGROUND:Conditional survival (CS) measures the probability that patients will survive an additional number of years given that they have already survived for a certain period of time. METHODS:In total, 2935 gastric cancer patients who had undergone curative gastrectomy between 1995 and 2011 were enrolled. The Cox p...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-015-2022-2
更新日期:2015-12-23 00:00:00
abstract:BACKGROUND:Breast cancer is the second leading cause of cancer deaths in women in the United States. Although the causes of this disease are incompletely understood, oxidative DNA damage is presumed to play a critical role in breast carcinogenesis. A common oxidatively induced DNA lesion is 8-hydroxyguanine (8-OH-Gua),...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-6-297
更新日期:2006-12-27 00:00:00
abstract:BACKGROUND:A major cause of disease-related death in nasopharyngeal carcinoma (NPC) is the development of distant metastasis (DM) despite combination chemoradiotherapy treatment. We previously identified and validated a four microRNA (miRNA) signature that is prognostic for DM. In this study, characterization of a key ...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-07081-z
更新日期:2020-06-26 00:00:00
abstract:BACKGROUND:Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs) stimulate neutrophil production and may reduce FN incidence when given prophylactically following...
journal_title:BMC cancer
pub_type: 杂志文章,meta分析,评审
doi:10.1186/1471-2407-11-404
更新日期:2011-09-23 00:00:00
abstract:BACKGROUND:Methylation of promoter region is the major mechanism affecting gene expression in tumors. Recent methylome studies of brain tumors revealed a list of new epigenetically modified genes. Our aim was to study promoter methylation of newly identified epigenetically silenced genes together with already known epi...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-12-218
更新日期:2012-06-06 00:00:00
abstract:BACKGROUND:Preclinical evidence suggests that aspirin may inhibit lung cancer progression. In a large cohort of lung cancer patients, we investigated whether low-dose aspirin use was associated with a reduction in the risk of lung cancer-specific mortality. METHODS:We identified lung cancer patients from English cance...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-015-1910-9
更新日期:2015-11-17 00:00:00
abstract:BACKGROUND:Colorectal cancer (CRC) is a heterogeneous disease with a complex biology and a wide number of altered genes such as BRAF, KRAS and PIK3CA. Advances with new-targeted therapies have been achieved and available treating options have prolonged patient's survival. However, BRAF-mutated CRC patients remain unres...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-6586-0
更新日期:2020-02-17 00:00:00
abstract:BACKGROUND:The epithelial-mesenchymal transition (EMT) plays a pivotal role in various physiological processes, such as embryonic development, tissue morphogenesis, and wound healing. EMT also plays an important role in cancer invasion, metastasis, and chemoresistance. Additionally, EMT is partially responsible for che...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-07615-5
更新日期:2020-11-23 00:00:00
abstract:BACKGROUND:Colon cancer is the most common type of gastrointestinal cancer and has high morbidity and mortality. Colon adenocarcinoma (COAD) is the main pathological type of colon cancer, and much evidence has supported the correlation between the prognosis of COAD and the immune system. The current study aimed to deve...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-07532-7
更新日期:2020-11-09 00:00:00