Peripheral lymph node stromal cells can promote growth and tumorigenicity of breast carcinoma cells through the release of IGF‐I and EGF

LeBedis, Christina A.; Chen, Keguan; Fallavollita, Lucia; Boutros, Tarek; Brodt, Pnina

doi:10.1002/ijc.10481

Cited by 75 publications

(44 citation statements)

References 52 publications

(52 reference statements)

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“…With regard to growth factors, IGFs and epidermal growth factors (EGF) activate the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathways, which alter Jun and Fos activities at the PR promoter and decrease its ER-mediated transcription (45). LN stromal cells produce both IGF and EGF (41), which may explain the reduced PR induction as well as the reduced estradiol regulation of other target genes at this site. Increased cortactin levels (Fig.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Insensitivity in a Model of Estrogen Receptor–Positive Breast Cancer Lymph Node Metastasis

Harrell

Dye²,

Harvell³

et al. 2007

Cancer Research

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The lymphatic system is a common avenue for the spread of breast cancer cells and dissemination through it occurs at least as frequently as hematogenous metastasis. Approximately 75% of primary breast cancers are estrogen receptor (ER) positive and the majority of these maintain receptor expression as lymph node (LN) metastases. However, it is unknown if ER function is equivalent in cancer cells growing in the breast and in the LNs. We have developed a model to assess estrogen responsiveness in ER + breast tumors and LN metastases. Fluorescent ER + MCF-7 tumors were grown in ovariectomized nude mice supplemented with estradiol. Once axillary LN metastasis arose, estradiol was withdrawn (EWD), for 1 or 4 weeks, or continued, to assess estradiol responsiveness. On EWD, proliferation rates fell similarly in tumors and LN metastases. However, estradiol-dependent ER down-regulation and progesterone receptor induction were deficient in LN metastases, indicating that ER-dependent transcriptional function was altered in the LN. Cancer cells from estradioltreated and EWD primary tumors and matched LN metastases were isolated by laser capture microdissection. Global gene expression profiling identified transcripts that were regulated by the tissue microenvironment, by hormones, or by both. Interestingly, numerous genes that were estradiol regulated in tumors lost estradiol sensitivity or were regulated in the opposite direction by estradiol in LN metastases. We propose that the LN microenvironment alters estradiol signaling and may contribute to local antiestrogen resistance. [Cancer Res 2007;67(21):10582-91]

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Section: Discussionmentioning

confidence: 99%

Estrogen Insensitivity in a Model of Estrogen Receptor–Positive Breast Cancer Lymph Node Metastasis

Harrell

Dye²,

Harvell³

et al. 2007

Cancer Research

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“…It has recently been shown that estrogen regulates the BCSC population through a paracrine mechanism involving FGF9 (44). Additional factors produced by cells in the tumor microenvironment regulate tumor proliferation, invasion, and metastasis; these include IGF, PDGF, Wnt, Notch ligand, Hedgehog ligands, and MMPs (45)(46)(47)(48)(49)(50).…”

Section: Figurementioning

confidence: 99%

Breast cancer stem cells, cytokine networks, and the tumor microenvironment

Korkaya¹,

Liu²,

2011

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Many tumors, including breast cancer, are maintained by a subpopulation of cells that display stem cell properties, mediate metastasis, and contribute to treatment resistance. These cancer stem cells (CSCs) are regulated by complex interactions with the components of the tumor microenvironment -including mesenchymal stem cells, adipocytes, tumor associated fibroblasts, endothelial cells, and immune cells -through networks of cytokines and growth factors. Since these components have a direct influence on CSC properties, they represent attractive targets for therapeutic development.

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“…Several additional data and converging evidence support the concept that the HER family [epidermal growth factor (EGF) receptor (EGFR), HER-2, HER-3, and HER-4] and their ligands can contribute to breast cancer development and clinical course of the disease (6). Abnormal expression of HER members results in receptor hyperactivation due to abnormal transcriptional regulation ensuing in protein overexpression and stimulation enhancement by growth factors (7). Although the functionality of HER members, especially HER-2, has been extensively studied in breast cancer (6), the pathologic conditions resulting in HER member family activation is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Expression of Neurotensin and NT1 Receptor in Human Breast Cancer: A Potential Role in Tumor Progression

et al. 2006

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Emerging evidence supports neurotensin as a trophic and antiapoptotic factor, mediating its control via the highaffinity neurotensin receptor (NT1 receptor) in several human solid tumors. In a series of 51 patients with invasive ductal breast cancers, 34% of all tumors were positive for neurotensin and 91% positive for NT1 receptor. We found a coexpression of neurotensin and NT1 receptor in a large proportion (30%) of ductal breast tumors, suggesting a contribution of the neurotensinergic signaling cascade within breast cancer progression. Functionally expressed NT1 receptor, in the highly malignant MDA-MB-231 human breast cancer cell line, coordinated a series of transforming functions, including cellular migration, invasion, induction of the matrix metalloproteinase (MMP)-9 transcripts, and MMP-9 gelatinase activity. Disruption of NT1 receptor signaling by silencing RNA or use of a specific NT1 receptor antagonist, SR48692, caused the reversion of these transforming functions and tumor growth of MDA-MB-231 cells xenografted in nude mice. Our findings support the contribution of neurotensin in human breast cancer progression and point out the utility to develop therapeutic molecules targeting neurotensin or NT1 receptor signaling cascade. These strategies would increase the range of therapeutic approaches and be beneficial for specific patients. (Cancer Res 2006; 66(12): 6243-9)

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Peripheral lymph node stromal cells can promote growth and tumorigenicity of breast carcinoma cells through the release of IGF‐I and EGF

Cited by 75 publications

References 52 publications

Estrogen Insensitivity in a Model of Estrogen Receptor–Positive Breast Cancer Lymph Node Metastasis

Estrogen Insensitivity in a Model of Estrogen Receptor–Positive Breast Cancer Lymph Node Metastasis

Breast cancer stem cells, cytokine networks, and the tumor microenvironment

Expression of Neurotensin and NT1 Receptor in Human Breast Cancer: A Potential Role in Tumor Progression

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