Carcinoma-associated fibroblasts provide operational flexibility in metastasis

Wever, Olivier De; Bockstal, Mieke Van; Mareel, Marcus; Hendrix, An; Bracke, Marc

doi:10.1016/j.semcancer.2013.12.009

Cited by 104 publications

(90 citation statements)

References 166 publications

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“…Cancer cells exist within a complex ecosystem consisting of CAFs, endothelial cells, and immune cells, and actively interact with the adjacent tumor microenvironment to promote cancer growth, survival, and metastasis [19]. Increasing histopathological evidence indicates that tumor-associated stroma, especially CAFs, may refine the prognostic assessment of breast cancer [2].…”

Section: Discussionmentioning

confidence: 99%

Galectin-1 knockdown in carcinoma-associated fibroblasts inhibits migration and invasion of human MDA-MB-231 breast cancer cells by modulating MMP-9 expression

Zhu¹,

Wang²,

Zhang³

et al. 2016

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Carcinoma-associated fibroblasts (CAFs) play central roles in facilitating tumor progression and metastasis in breast cancer. Galectin-1 (Gal-1), a marker of CAFs, was previously reported to be associated with tumorigenesis and metastasis of various types of tumors. The aim of this study is to investigate the role of Gal-1 in CAF-mediated breast cancer metastasis and its underlying molecular mechanisms. Our results showed that CAFs isolated from human breast tumor tissues expressed higher level of Gal-1 compared with paired normal fibroblasts, and the conditioned medium (CM) of CAFs significantly induced the migration and invasion of human MDA-MB-231 breast cancer cells. Knockdown of Gal-1 in CAFs dramatically inhibited CAF-CM-induced cell migration and invasion, probably by inhibiting the expression of matrix metalloprotein 9 (MMP-9). Our findings demonstrate that Gal-1-regulated CAFs activation promotes breast cancer cell metastasis by upregulating MMP-9 expression, which indicated that Gal-1 in CAFs might be a potential novel target for breast cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Galectin-1 knockdown in carcinoma-associated fibroblasts inhibits migration and invasion of human MDA-MB-231 breast cancer cells by modulating MMP-9 expression

Zhu¹,

Wang²,

Zhang³

et al. 2016

ABBS

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“…This inhibits downstream intercellular signalling of the receptor [43]. The VEGF, FGF and PDGF family proteins are abundantly present in the tumourenvironment as they are secreted as well by cancer cells, CAFs and tumour-associated macrophages (TAMs) [21,22,24,60]. The receptors are expressed on the cell membrane of cancer cells, CAFs, TAMs and endothelial cells.…”

Section: Cafs As a Target In Cancer Therapymentioning

confidence: 99%

Cancer-associated fibroblasts as target and tool in cancer therapeutics and diagnostics

et al. 2015

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Cancer-associated fibroblasts (CAFs) are drivers of tumour progression and are considered as a target and a tool in cancer diagnostic and therapeutic applications. An increased abundance of CAFs or CAF signatures are recognized as a bad prognostic marker in several cancer types. Tumour-environment biomimetics strongly improve our understanding of the communication between CAFs, cancer cells and other host cells. Several experimental drugs targeting CAFs are in clinical trials for multiple tumour entities; alternatively, CAFs can be exploited as a tool to characterize the functionality of circulating tumour cells or to capture them as a tool to prevent metastasis. The continuous interaction between tissue engineers, biomaterial experts and cancer researchers creates the possibility to biomimic the tumour-environment and provides new opportunities in cancer diagnostics and management.

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“…Factor shape was calculated as (perimeter) 2 /(4 Â p Â area) for quantification. MCF-7, T47D, and MDA MB 231 type I collagen gel invasion assays are performed and quantified as described in Supplementary Materials and Methods and ref.…”

Section: Functional Assaysmentioning

confidence: 99%

“…Cancer progression is the result of a complex interaction between the cancer cells and their microenvironment (1,2).…”

Section: Introductionmentioning

confidence: 99%

Cancer-Associated Adipose Tissue Promotes Breast Cancer Progression by Paracrine Oncostatin M and Jak/STAT3 Signaling

et al. 2014

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Increasing evidence supports the critical roles played by adipose tissue in breast cancer progression. Yet, the mediators and mechanisms are poorly understood. Here, we show that breast cancer-associated adipose tissue from freshly isolated tumors promotes F-actin remodeling, cellular scattering, invasiveness, and spheroid reorganization of cultured breast cancer cells. A combination of techniques, including transcriptomics, proteomics, and kinomics enabled us to identify paracrine secretion of oncostatin M (OSM) by cancer-associated adipose tissue. Specifically, OSM, expressed by CD45 þ leucocytes in the stromal vascular fraction, induced phosphorylation of STAT3 (pSTAT3-)Y705 and S727 in breast cancer cells and transcription of several STAT3-dependent genes, including S100 family members S100A7, S100A8, and S100A9. Autocrine activation of STAT3 in MCF-7 cells ectopically expressing OSMinduced cellular scattering and peritumoral neovascularization of orthotopic xenografts. Conversely, selective inhibition of OSM by neutralizing antibody and Jak family kinases by tofacitinib inhibited STAT3 signaling, peritumoral angiogenesis, and cellular scattering. Importantly, nuclear staining of pSTAT3-Y705 identified at the tumor invasion front in ductal breast carcinomas correlates with increased lymphovascular invasion. Our work reveals the potential of novel therapeutic strategies targeting the OSM and STAT3 axis in patients with breast cancer harboring nuclear pSTAT3-Y705. Cancer Res; 74(23);

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Carcinoma-associated fibroblasts provide operational flexibility in metastasis

Cited by 104 publications

References 166 publications

Galectin-1 knockdown in carcinoma-associated fibroblasts inhibits migration and invasion of human MDA-MB-231 breast cancer cells by modulating MMP-9 expression

Galectin-1 knockdown in carcinoma-associated fibroblasts inhibits migration and invasion of human MDA-MB-231 breast cancer cells by modulating MMP-9 expression

Cancer-associated fibroblasts as target and tool in cancer therapeutics and diagnostics

Cancer-Associated Adipose Tissue Promotes Breast Cancer Progression by Paracrine Oncostatin M and Jak/STAT3 Signaling

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