Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion

Zhang, Yuan; Tang, Huijuan; Cai, Jing; Zhang, Ting; Guo, Jianfeng; Feng, Da; Wang, Zehua

doi:10.1016/j.canlet.2011.01.011

Cited by 210 publications

(171 citation statements)

References 24 publications

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“…This marker has previously been found to be associated with tumor stage, and lymph node and omental metastasis in patients with EOC treated with standard surgery followed by chemotherapy, but again, no data on the association between αSMA expression and tumor outcome has been reported [26]. In our series, the high percentage of cases expressing αSMA limited our ability to perform statistical analyses.…”

Section: Discussionmentioning

confidence: 61%

“…In our series, the high percentage of cases expressing αSMA limited our ability to perform statistical analyses. Nearly every tumor treated with neoadjuvant chemotherapy expressed αSMA, a much greater frequency of positive cases than a previous report which only found around 20 % of advanced stage, chemonaïve EOCs expressing αSMA [26]. The point of divergence between these two studies is neoadjuvant chemotherapy, either its inclusion or exclusion in patient management.…”

Section: Discussionmentioning

confidence: 68%

“…Tumor-associated stromal expression of FAP was found to be associated with more aggressive disease progression, and potential development of metastasis, recurrence, and death in colon and pancreatic cancers [23][24][25]. Previous studies in ovarian cancers treated with standard surgery followed by chemotherapy showed an association of FAP with advanced stage disease, lymph node metastasis, omental involvement, lymphovascular disease, and increased angiogenesis, but there is lack of data on the association of FAP with patient outcomes [26]. In our series of 66 patients treated with neoadjuvant therapy followed by debulking surgery, FAP was expressed in 86 % of cases, other study showed FAP expression in 91 % of chemonaive ovarian cancer [26].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies in ovarian cancers treated with standard surgery followed by chemotherapy showed an association of FAP with advanced stage disease, lymph node metastasis, omental involvement, lymphovascular disease, and increased angiogenesis, but there is lack of data on the association of FAP with patient outcomes [26]. In our series of 66 patients treated with neoadjuvant therapy followed by debulking surgery, FAP was expressed in 86 % of cases, other study showed FAP expression in 91 % of chemonaive ovarian cancer [26]. Furthermore, we found that FAP expression by tumor-associated stroma was associated with higher recurrence rates.…”

Section: Discussionmentioning

confidence: 99%

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Clinical Implications of Marker Expression of Carcinoma-Associated Fibroblasts (CAFs) in Patients with Epithelial Ovarian Carcinoma After Treatment with Neoadjuvant Chemotherapy

Mhawech‐Fauceglia

Wang

Samrao

et al. 2013

Cancer Microenvironment

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Cancer-associated fibroblasts (CAFs) play an important role in tumor initiation and progression. The aim of this study is to explore the role of 2 CAF markers, fibroblast activated protein (FAP) and α-smooth muscle actin (αSMA), in patients with epithelial ovarian cancer (EOC) post-neoadjuvant chemotherapy. Sixty-six patients with the diagnosis of EOC treated with debulking surgery after neoadjuvant therapy were retrieved from the archives. Immunohistochemistry for FAP and αSMA antibodies were performed on paraffin-embedded tissue. αSMA was expressed by tumor-associated stroma in 95 % of cases and by tumor cells in 9 % of cases. No statistical power was found for αSMA and disease status. Our data indicate that FAP plays an important role in predicting tumor aggressiveness in patients with EOC post-neoadjuvant therapy, and its frequent expression in this malignancy implicates that FAP targeted therapy could be a very attractive strategy.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Clinical Implications of Marker Expression of Carcinoma-Associated Fibroblasts (CAFs) in Patients with Epithelial Ovarian Carcinoma After Treatment with Neoadjuvant Chemotherapy

Mhawech‐Fauceglia

Wang

Samrao

et al. 2013

Cancer Microenvironment

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“…Recently, their major role in shaping the local microenvironment around a growing tumor was shown in numerous studies (3)(4)(5). As a result, fibroblasts can affect the ability of cancer cells to metastasize (6)(7)(8) and conversely, the ability of the immune system to find and attack those cells (9).…”

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confidence: 99%

On the mechanism of long-range orientational order of fibroblasts

Balagam

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Long-range alignment ordering of fibroblasts have been observed in the vicinity of cancerous tumors and can be recapitulated with in vitro experiments. However, the mechanisms driving their ordering are not understood. Here, we show that local collisiondriven nematic alignment interactions among fibroblasts are insufficient to explain observed long-range alignment. One possibility is that there exists another orientation field coevolving with the cells and reinforcing their alignment. We propose that this field reflects the mechanical cross-talk between the fibroblasts and the underlying fibrous material on which they move. We show that this long-range interaction can give rise to high nematic order and to the observed patterning of the cancer microenvironment.alignment | fibroblasts | long-range order | extracellular matrix | collagen fibers F ibroblasts are spindle-shaped cells that are highly motile and are involved in many critical biological processes, such as wound healing (1, 2). Recently, their major role in shaping the local microenvironment around a growing tumor was shown in numerous studies (3-5). As a result, fibroblasts can affect the ability of cancer cells to metastasize (6-8) and conversely, the ability of the immune system to find and attack those cells (9).An isolated fibroblast moves back and forth on coverslips for over 60 h without significant change of the direction of its major axis (10). Typically, those fibroblasts are in a spindle shape with an aspect ratio from two to five. Apart from steric constraints, fibroblasts barely interact with each other (10). Curiously, imaging of tumor microenvironments often indicates longrange ordering of fibroblasts. This order often takes the form of circumferential alignment of the cells in a region surrounding the cancer cells (11,12). The mechanisms that lead to this ordering are not well-understood.Notably, a similar ordering can be observed for underlying collagen fibers (6, 13). Collagen fibers are the main structural component in the extracellular space of various normal connective tissues and play a significant role in local cancer cell invasion and in metastasis (14). Aligned fibers perpendicular to the boundary cancer cell clusters facilitate local invasions of cancer cells, and conversely, aligned fibers parallel to the tumor boundary may restrict the migration of cancer cells. Furthermore, the circumferential collagen fiber structure has been hypothesized to be responsible for the observed separation between immune and cancer cells (13). Specifically, ex vivo assays indicate that the migration of tumor-killing CD8 + T cells is reduced where dense collagen fibers form conduit-like structures (15). Therefore, understanding the mechanism of the pattern formation of fibroblasts and collagen fibers in the cancer microenvironment is important to strike a balance between constraining cancer cell from invasion and enabling the infiltration of cancer-killing immune cells.In vivo experimental observation of this pattern formation dynamically is techn...

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Microenvironmental modulation of the developing tumour: an immune‐stromal dialogue

2020

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Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion

Cited by 210 publications

References 24 publications

Clinical Implications of Marker Expression of Carcinoma-Associated Fibroblasts (CAFs) in Patients with Epithelial Ovarian Carcinoma After Treatment with Neoadjuvant Chemotherapy

Clinical Implications of Marker Expression of Carcinoma-Associated Fibroblasts (CAFs) in Patients with Epithelial Ovarian Carcinoma After Treatment with Neoadjuvant Chemotherapy

On the mechanism of long-range orientational order of fibroblasts

Microenvironmental modulation of the developing tumour: an immune‐stromal dialogue

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