Studying primary tumor–associated fibroblast involvement in cancer metastasis in mice

Duyverman, Annique M.; Steller, Ernst J.A.; Jain, Rakesh K.; Duda, Dan G.

doi:10.1038/nprot.2012.031

Cited by 18 publications

(15 citation statements)

References 30 publications

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“…Here, CAFs in co‐culture with epithelial tumour cells exhibit significantly larger tumour volumes and faster growth rates compared with xenografts of tumour cells alone . Additionally, xenograft co‐culture models exhibit strong pro‐inflammatory and angiogenic paracrine signalling, with the CAF component promoting metastatic deposition of circulating tumour fragments . CAF‐induced functional alterations are thought to occur in the leading edge of lung cancer cells, promoting not only their invasive capacity, but also their proliferative potential.…”

Section: Cafs In Lung Cancermentioning

confidence: 99%

The role of stromal fibroblasts in lung carcinogenesis: A target for chemoprevention?

et al. 2015

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The tumour microenvironment plays an essential role in the development and spread of cancers. Tumour cells interact with the surrounding extracellular matrix (ECM), embedded within which, are a variety of non‐cancer cells including cells of the vasculature, immune system and fibroblasts. The essential role of fibroblasts in the cultivation and maintenance of an environment in which tumour cells are able to maintain their aggressive phenotypic traits is becoming increasingly well documented. Cancer‐associated fibroblasts are able to secrete a vast array of ECM‐modulating factors, meaning that they have potential for a functional role in every step of the carcinogenic process. In particular, they are likely to have a role in early tumour‐initiating inflammatory events, and so may provide a potential target for chemopreventive intervention. This review summarises the known interactions between lung tumour cells and surrounding reactive fibroblasts, highlighting the need to further investigate cancer‐associated fibroblasts as therapeutic targets in lung cancer chemoprevention strategies.

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Section: Cafs In Lung Cancermentioning

confidence: 99%

The role of stromal fibroblasts in lung carcinogenesis: A target for chemoprevention?

et al. 2015

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“…Fibroblasts are among the major stromal cells in the tumor microenvironment and its functions include the deposition of ECM, regulation of epithelial differentiation, regulation of inflammation, and involvement in wound healing 1–4. The fibroblasts involved in primary tumor formation and invasion are referred to as cancer associated fibroblasts (CAFs) 3–6. The presence of invasive tumor cells stimulates resident stromal fibroblasts and alters gene and protein expression that promotes the invasive capacity of tumor cells 5–7.…”

Section: Introductionmentioning

confidence: 99%

Cell behavior observation and gene expression analysis of melanoma associated with stromal fibroblasts in a three‐dimensional magnetic cell culture array

Okochi

Matsumura

Yamamoto

et al. 2012

Biotechnology Progress

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A three-dimensional (3D) multicellular tumor spheroid culture array has been fabricated using a magnetic force-based cell patterning method, analyzing the effect of stromal fibroblast on the invasive capacity of melanoma. Formation of spheroids was observed when array-like multicellular patterns of melanoma were developed using a pin-holder device made of magnetic soft iron and an external magnet, which enables the assembly of the magnetically labeled cells on the collagen gel-coated surface as array-like cell patterns. The interaction of fibroblast on the invasion of melanoma was investigated using three types of cell interaction models: (i) fibroblasts were magnetically labeled and patterned together in array with melanoma spheroids (direct-interaction model), (ii) fibroblasts coexisting in the upper collagen gel (indirect-interaction model) of melanoma spheroids, and (iii) fibroblast-sheets coexisting under melanoma spheroids (fibroblast-sheet model). The fibroblast-sheet model has largely increased the invasive capacity of melanoma, and the promotion of adhesion, migration, and invasion were also observed. In the fibroblast-sheet model, the expression of IL-8 and MMP-2 increased by 24-fold and 2-fold, respectively, in real time RT-PCR compared to the absence of fibroblasts. The results presented in this study demonstrate the importance of fibroblast interaction to invasive capacity of melanoma in the 3D in vitro bioengineered tumor microenvironment.

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“…We have used this model—together with an isolated tumor perfusion model and a spontaneous metastases model where we can selectively deplete carcinoma-associated fibroblasts 29,30 —to unravel the role of passenger fibroblasts in tumor metastasis to the lungs 13 .…”

Section: Introductionmentioning

confidence: 99%

“…The parabiosis skin transplantation model described here mimics the steps of spontaneous metastases from tumor shedding up to the outgrowth of micrometastases, taking advantage of the fluorescent labeling of the passenger stromal cells. Last, to facilitate depletion of the stromal compartment of the tumor microenvironment without affecting other organs, we developed a model of selective depletion of human carcinoma-associated fibroblasts 29 .…”

Section: Introductionmentioning

confidence: 99%

A transient parabiosis skin transplantation model in mice

et al. 2012

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Parabiosis—conjoined surgery to provide a shared circulation between two mice—has been previously developed to study the hematopoietic system. This protocol describes the use of parabiosis for efficient transplantation of skin from a transgenic to a wild-type mouse. It can be used to study the role of stromal cells in a spontaneous model of distant cancer dissemination (metastasis). We have recently shown that primary tumor-derived stromal cells may facilitate metastasis by providing a provisional stroma at the secondary site. Studying the role of primary tumor–derived stroma cells requires methods for distinguishing and targeting stromal cells originating from the primary tumor versus their counterparts in the metastatic site. Parabiosis may also be used, taking advantage of the shared circulation between the parabiosed mice, to study tumor metastasis from one parabiont to another, or to investigate the role of circulating inflammatory cells or stem cells. Studying the role of stromal cells in metastasis using this model typically takes up to 11 weeks.

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Studying primary tumor–associated fibroblast involvement in cancer metastasis in mice

Cited by 18 publications

References 30 publications

The role of stromal fibroblasts in lung carcinogenesis: A target for chemoprevention?

The role of stromal fibroblasts in lung carcinogenesis: A target for chemoprevention?

Cell behavior observation and gene expression analysis of melanoma associated with stromal fibroblasts in a three‐dimensional magnetic cell culture array

A transient parabiosis skin transplantation model in mice

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