Bone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction

Ishii, Genichiro; Sangai, Takafumi; Oda, Tatsuya; Aoyagi, Yasuyuki; Hasebe, Takahiro; Kanomata, Naoki; Endoh, Yasushi; Okumura, C.; Okuhara, Yoko; Magae, Junji; Emura, M.; Ochiya, Takahiro; Ochiai, Atsushi

doi:10.1016/s0006-291x(03)01544-4

Cited by 251 publications

(186 citation statements)

References 32 publications

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“…Bone marrow-derived MSC's contribute to 25% of the total myofibroblast population in the tumor stroma in a mouse model of pancreatic insulinoma 33 and in a subcutaneous pancreatic xenograft tumor. 34 Furthermore, these bone marrow-derived MSC-derived myofibroblasts actively participate in the production of matrix proteins, such as collagen Type I, in xenograft tumors. 35 Once integrated in the stroma, human bone marrow-derived MSC's cause the cancer cells to increase their metastatic potency.…”

Section: Characterization and Origin Of A Myofibroblastmentioning

confidence: 99%

Stromal myofibroblasts are drivers of invasive cancer growth

Wever¹,

Demetter²,

Mareel³

et al. 2008

Intl Journal of Cancer

625

601

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Tissue integrity is maintained by the stroma in physiology. In cancer, however, tissue invasion is driven by the stroma. Myofibroblasts and cancer-associated fibroblasts are important components of the tumor stroma. The origin of myofibroblasts remains controversial, although fibroblasts and bone marrow-derived precursors are considered to be the main progenitor cells. Myofibroblast reactions also occur in fibrosis. Therefore, we wonder whether nontumorous myofibroblasts have different characteristics and different origins as compared to tumor-associated myofibroblasts. The mutual interaction between cancer cells and myofibroblasts is dependent on multiple invasive growth-promoting factors, through direct cell-cell contacts and paracrine signals. Since fibrosis is a major side effect of radiotherapy, we address the question how the main methods of cancer management, including chemotherapy, hormonotherapy and surgery affect myofibroblasts and by inference the surrogate endpoints invasion and metastasis.

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Section: Characterization and Origin Of A Myofibroblastmentioning

confidence: 99%

Stromal myofibroblasts are drivers of invasive cancer growth

Wever¹,

Demetter²,

Mareel³

et al. 2008

Intl Journal of Cancer

625

601

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“…(25,28,39) Although the origin of CAFs has not been clarified, at least some have been suggested to be bone-marrow derived. (40,41) Further studies will reveal the relationship between aromataseexpressing fibroblasts and CAFs, and the mechanism by which normal fibroblasts convert to CAFs.…”

Section: Estrogen Signaling In the Cancer Microenvironmentmentioning

confidence: 99%

Estrogen signaling pathway and its imaging in human breast cancer

2009

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Recent remarkable progress in hormonal therapy has provided great benefit to breast cancer patients, but it also evokes novel issues: how accurately can the efficacy of each hormonal therapy be predicted and how can hormonal therapy-resistant patients be treated? These clinically important issues must be closely related to the biological events in each cancer, such as the alteration of intracellular multiple estrogen signaling pathways and the estrogen-related cancer microenvironment, which has recently revealed by molecular biological studies on estrogen and its receptors. However, the estrogen signaling status in individual breast cancers has not been clarified yet. Here we present the context of these issues and introduce our study of new tools which enable the visualization of estrogen signals in individual cancers. The assessment of estrogen receptor (ER)-a activity in individual cancers or ER-activating ability of the cancer microenvironment in each breast cancer patient revealed several new findings and interesting observations. We hope that these approaches provide new clues about the estrogen-dependent mechanisms of breast cancer development, and will be useful to advance the diagnosis and treatment of breast cancer patients. (Cancer Sci 2009; 100: 1773-1778) Estrogen receptor and hormonal therapy in breast cancer E strogen controls various physiological functions in many target tissues, and is also involved in diseases such as breast cancer, endometrial cancer, vascular disease, osteoporosis, and others. In particular, breast cancer is well recognized to be a crucial tumor in which estrogen and its receptor (ER) regulate development and progression in most cases, and are therefore the most important and effective targets for the therapy of breast cancer.(1) In this article, ER refers to estrogen receptor α unless specified.The efficacy of hormonal therapies targeting estrogen and ER has been established in numerous clinical trials. Current hormonal therapies are performed by two main strategies: inhibition of ER functions by anti-estrogens and deprivation of estrogen production by luteinizing hormone-releasing hormone agonist (pre-menopause) or aromatase inhibitor (post-menopause). Prediction of the efficiency of these therapies has involved using classical molecular biomarkers such as ERα and progesterone receptor.(2) However, approximately one-third of ER-positive patients do not respond to endocrine therapy, while some ER-negative patients are responsive.(3) These discrepancies could result from different estrogenrelated intracellular signaling pathways in breast cancer cells.One of the approaches to analyze the estrogen signaling status in breast cancer is expression profiling of estrogen-regulated genes in cancer cells. Comprehensive gene expression analysis, such as DNA microarray, may be a useful tool to address this issue. So far, we have analyzed estrogen-responsive gene expression profiles among ER-positive cancer cells using comprehensive DNA microarray (4) and, based on the obtained informa...

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“…For reprints contact: Reprints@AlphaMedPress.com 700 Bone Marrow-Derived Fibroblasts Recruited into Fibrotic Lesions transplantation of bone marrow (BM), hematopoietic stem cells or nonhematopoietic mesenchymal stem cells, muscle [7][8][9][10][11], heart [12][13][14], liver [15][16][17][18][19], vascular cells [20,21], and other mesenchymal cells [22][23][24] of donor origin have been detected. Investigators revealed that BM-derived cells can be progenitors for tissue fibroblasts that are recruited through the circulation to populate peripheral organs [25][26][27][28][29]. During renal fibrosis, a small number of fibroblasts were BM origin using BM chimera and transgenic reporter mice [25].…”

Section: Introductionmentioning

confidence: 99%

“…During renal fibrosis, a small number of fibroblasts were BM origin using BM chimera and transgenic reporter mice [25]. We previously reported that cancer-induced stroma generated by the human pancreatic cancer cell line consist of BM-derived fibroblasts and that BM-derived fibroblasts become a major component of cancer-induced stromal cells in the later stage of tumor development [26]. Furthermore, BM-derived fibroblasts were engrafted into multiple organs, and it was found that these cells are recruited into injured tissue [27,28].…”

Section: Introductionmentioning

confidence: 99%

In Vivo Characterization of Bone Marrow–Derived Fibroblasts Recruited into Fibrotic Lesions

et al. 2005

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Fibroblasts, which are widely distributed and play a key part in tissue fibrosis, are phenotypically and functionally heterogeneous. Recent studies reported that bone marrow can be a source of tissue fibroblast. In the study reported here, we investigated in vivo characterization of bone marrowderived fibroblasts recruited into various fibrotic lesions. Mice were engrafted with bone marrow isolated from transgenic mice expressing green fluorescent protein (GFP), and fibrotic lesions were induced by cancer implantation (skin), excisional wounding (skin), and bleomycin administration (lung). A small population of GFP + fibroblast was found even in nonfibrotic skin (8.7% ± 4.6%) and lung (8.9% ± 2.5%). The proportion of GFP + fibroblasts was significantly increased after cancer implantation (59.7% ± 16.3%) and excisional wounding (32.2% ± 4.8%), whereas it was not elevated after bleomycin administration (7.1% ± 2.4%). Almost all GFP + fibroblasts in fibrotic lesions expressed type I collagen, suggesting that bone marrow-derived fibroblasts would contribute to tissue fibrosis. GFP + fibroblasts expressed CD45, Thy-1, and α-smooth muscle actin at various proportions. Our results suggested that bone marrow-derived fibroblasts expressed several fibroblastic markers in vivo and could be efficiently recruited into fibrotic lesions in response to injurious stimuli; however, the degree of recruitment frequency might depend on the tissue microenvironment. Stem Cells 2005;23:699-706

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Bone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction

Cited by 251 publications

References 32 publications

Stromal myofibroblasts are drivers of invasive cancer growth

Stromal myofibroblasts are drivers of invasive cancer growth

Estrogen signaling pathway and its imaging in human breast cancer

In Vivo Characterization of Bone Marrow–Derived Fibroblasts Recruited into Fibrotic Lesions

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