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A Zebrafish Model D...
A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated Cancer Metastasis
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- Liu, Caifeng (author)
- Karolinska Institute, Sweden; Shandong University, Peoples R China
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- Zhang, Yunjian (author)
- Karolinska Institute, Sweden; Sun Yat Sen University, Peoples R China
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- Lim, Sharon (author)
- Karolinska Institute, Sweden
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- Hosaka, Kayoko (author)
- Karolinska Institutet
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- Yang, Yunlong (author)
- Karolinska Institutet
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- Pavlova, Tatiana (author)
- Karolinska Institutet
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- Alkasalias, Twana (author)
- Karolinska Institutet
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- Hartman, Johan (author)
- Karolinska Institutet
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- Jensen, Lasse (author)
- Linköpings universitet,Avdelningen för kardiovaskulär medicin,Medicinska fakulteten,Region Östergötland, Klinisk farmakologi,Karolinska Institute, Sweden
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- Xing, Xiaoming (author)
- Qingdao University, Peoples R China; Qingdao University, Peoples R China
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- Wang, Xinsheng (author)
- Qingdao University, Peoples R China; Qingdao University, Peoples R China
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- Lu, Yongtian (author)
- Shenzhen University, Peoples R China
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- Nie, Guohui (author)
- Shenzhen University, Peoples R China
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- Cao, Yihai (author)
- Karolinska Institute, Sweden; Shenzhen University, Peoples R China; Qingdao University, Peoples R China; Qingdao University, Peoples R China
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(creator_code:org_t)
- AMER ASSOC CANCER RESEARCH, 2017
- 2017
- English.
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In: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 23:16, s. 4769-4779
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Purpose: Cancer metastasis can occur at the early stage of tumor development when a primary tumor is at the microscopic size. In particular, the interaction of malignant cells with other cell types including cancer-associated fibroblasts (CAF) in promoting metastasis at the early stage of tumor development remains largely unknown. Here, we investigated the role of CAFs in facilitating the initial events of cancer metastasis when primary tumors were at microscopic sizes. Experimental Design: Multicolor-coded cancer cells and CAFs were coimplanted into the transparent zebrafish body and metastasis at a single-cell level was monitored in living animals. Healthy fibroblasts, tumor factor-educated fibroblasts, and CAFs isolated from various tumors were tested for their ability to facilitate metastasis. Results: We showed that CAFs promoted cancer cell metastasis at the very early stage during primary tumor development. When a primary tumor was at the microscopic size consisting of a few hundred cells, CAFs were able to hijack cancer cells for dissemination from the primary site. Surprisingly, a majority of metastatic cancer cells remained in tight association with CAFs in the circulation. Furthermore, stimulation of non-metastasis-promoting normal fibroblasts with TGF-B, FGF-2, HGF, and PDGF-BB led to acquisition of their metastatic capacity. Conclusions: Cancer metastasis occurs at the very early stage of tumor formation consisting of only a few hundred cells. CAFs are the key cellular determinant for metastasis. Our findings provide novel mechanistic insights on CAFs in promoting cancer metastasis and targeting CAFs for cancer therapy should be aimed at the early stage during cancer development. (C) 2017 AACR.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Liu, Caifeng
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Zhang, Yunjian
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Lim, Sharon
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Hosaka, Kayoko
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Yang, Yunlong
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Pavlova, Tatiana
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show more...
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Alkasalias, Twan ...
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Hartman, Johan
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Jensen, Lasse
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Xing, Xiaoming
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Wang, Xinsheng
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Lu, Yongtian
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Nie, Guohui
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Cao, Yihai
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Clinical Cancer ...
- By the university
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Linköping University
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Karolinska Institutet