Variations in stromal signatures in breast and colorectal cancer metastases

Webster, Jonathan; Beck, Andrew H.; Sharma, Mimansa; Espinosa, Íñigo; Weigelt, Britta; Schreuder, A.M.; Montgomery, Kelli; Jensen, Kristin C.; Rijn, Matt van de; West, Robert B.

doi:10.1002/path.2738

Cited by 33 publications

(28 citation statements)

References 19 publications

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“…These experimental data combined with the positive correlation between CSF-1 levels, macrophage recruitment and poor prognosis in human cancers (Scholl et al 1994;Leek and Harris 2002), together support the notion that macrophages and/or their products play a major role in facilitating late-stage metastatic progression of tumors (Lin et al 2001). Significantly a stromal CSF-1 gene expression signature in breast cancer correlated with poor outcomes and was observed to be similar between primary tumors and lymph node metastases (Webster et al 2010).…”

Section: Leukocytes In Mammary Development and Cancermentioning

confidence: 62%

Leukocytes in Mammary Development and Cancer

Coussens

Pollard

2010

Cold Spring Harbor Perspectives in Biology

171

137

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Section: Leukocytes In Mammary Development and Cancermentioning

confidence: 62%

Leukocytes in Mammary Development and Cancer

Coussens

Pollard

2010

Cold Spring Harbor Perspectives in Biology

171

137

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“…First, mainly due to poor experimental conduct, false (derived from another cell population within the cell culture than the one intended), cross-contaminated (with other human cells or cells from other species) and/or pathogen-(mycoplasm) contaminated cell lines have been discovered repeatedly. [9][10][11][12] Second, the representativeness of cultured cell lines as compared with the original tumors is being questioned as these cells have been cultured in the absence of stroma, 13 hence lacking the proper microenvironment and the original tissue architecture. Moreover during culturing, specific cells are continuously selected based on the in vitro conditions and cells might undergo additional ex vivo mutations.…”

mentioning

confidence: 99%

Functional characterization of osteosarcoma cell lines provides representative models to study the human disease

Mohseny

Machado

Cai

et al. 2011

Laboratory Investigation

164

151

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Cancer cell lines represent in vitro models for studying malignancies, general cell biology, drug discovery and more. Whether they can be considered as exact representative models of the parental tumors remains uncertain given the acquisition of additional ex vivo changes of the cells and the lack of tissue architecture and stroma. Previously, within the EuroBoNeT consortium, we characterized a collection of bone sarcoma cell lines on genomic and proteomic level. Here, we address the phenotypical and functional characterization of the unique set of osteosarcoma cell lines (n ¼ 19) in vitro and in vivo. For functional analysis of differentiation capacity, cells were stimulated towards osteoblasts, adipocytes and chondrocytes. Furthermore, all cell lines were injected subcutaneously and intramuscularly into nude mice to assay their in vivo tumor formation capacity as well as for phenotypical analysis of the tumors. All formed tumors were further characterized histologically and immunohistochemically. Out of 19 cell lines, 17 (89%) showed adipogenic differentiation, 13/19 (68%) could differentiate towards osteoblasts and in 6/19 (32%) cell lines chondrogenic differentiation was evident. About half of the cell lines (8/19, 42%) produced tumors in vivo after subcutaneous and intramuscular injections. Several cell lines showed invasion into adjacent tissues and one tumor developed several lung metastases. The use of cell lines, especially in cancer research, is of paramount importance. Here, we identify comprehensively characterized osteosarcoma cell lines, which robustly represent clinical osteosarcoma providing researchers useful in vitro and in vivo models to study the genetics and functional characteristics of this highly malignant neoplasm.

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“…Recently, a concordance between the CSF1 macrophage response signature in primary mammary and colorectal carcinomas and their corresponding lymph node metastases has been reported. 30 In a previous study, we also encountered a positive correlation between CD163-macrophages in primary endometrioid endometrial carcinomas and their matched lymph node metastases. 31 In the current study, we found that the expression of CSF1 by the tumor cells of primary endometrioid endometrial carcinomas is maintained in most metastatic tumors.…”

Section: Discussionmentioning

confidence: 99%

Stromal signatures in endometrioid endometrial carcinomas

et al. 2014

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The pattern of myometrial invasion in endometrioid endometrial carcinomas varies considerably; ie, from widely scattered glands and cell nests, often associated with a fibromyxoid stromal reaction (desmoplasia) and/ or a lymphocytic infiltrate, to invasive glands with little or no stromal response. Recently, two distinct stromal signatures derived from a macrophage response (colony-stimulating factor 1, CSF1) and a fibroblastic response (desmoid-type fibromatosis, DTF) were identified in breast carcinomas and correlated with clinicopathologic features including outcome. In this study, we explored whether these stromal signatures also apply to endometrioid carcinomas and how their expression patterns correlated with morphologic changes. We studied the stromal signatures both by immunohistochemistry and in situ hybridization in 98 primary endometrioid carcinomas with (87 cases) and without (11 cases) myometrial invasion as well as in the corresponding regional lymph nodes metatases of 9 myoinvasive tumors. Desmoplasia correlated positively with the DTF expression signature. Likewise, mononuclear infiltrates were found in the stroma of tumors expressing CSF1. Twenty-four out of eighty-seven (27%) myoinvasive endometrioid carcinomas were positive for the macrophage signature and thirteen out of eighty-seven (15%) expressed the fibroblast signature. Eleven additional cases were positive for both DTF and CSF1 signatures (11/87; 13%). However, over half of the cases (39/87; 45%) and the majority of the non-myoinvasive tumors (8/11; 73%) failed to express any of the two stromal signatures. The macrophage response (CSF1) was associated with higher tumor grade, lymphovascular invasion, and PIK3CA mutations (Po0.05). There was a concordance in the expression of the CSF1 signature in the primary tumors and their corresponding lymph node metastases. This study is the first characterization of stromal signatures in endometrioid carcinomas. Our findings shed new light on the relationship between genetically different endometrioid carcinomas and various stromal responses. Preservation of the CSF1 macrophage stromal response in the metastases leds support to targeting the CSF1 pathway in endometrioid endometrial carcinomas.

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Variations in stromal signatures in breast and colorectal cancer metastases

Cited by 33 publications

References 19 publications

Leukocytes in Mammary Development and Cancer

Leukocytes in Mammary Development and Cancer

Functional characterization of osteosarcoma cell lines provides representative models to study the human disease

Stromal signatures in endometrioid endometrial carcinomas

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