Mesenchymal stem cell-derived CCL-9 and CCL-5 promote mammary tumor cell invasion and the activation of matrix metalloproteinases

Swamydas, Muthulekha; Ricci, Krista; Rego, Stephen L.; Dréau, Didier

doi:10.4161/cam.25138

Cited by 65 publications

(45 citation statements)

References 60 publications

(85 reference statements)

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“…Down-regulation of CLEC12A in VHS, the more aggressive form of HS, is in line with previously published observations that such reduced function facilitates migratory capacity of myeloid cells in humans [46]. Down-regulation of CCL5 is in line with several studies in human cancers [37], [47], however contradictory to others [43]. Further investigations should focus on changes of gene function at protein level and a comparison of these histiocytic malignancies in dog and human.…”

Section: Discussionsupporting

confidence: 85%

The Two Main Forms of Histiocytic Sarcoma in the Predisposed Flatcoated Retriever Dog Display Variation in Gene Expression

et al. 2014

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Examination of gene functions in specific tumor types improves insight in tumorigenesis and helps design better treatments. Due to the rarity of histiocytic/dendritic cell sarcoma in humans, it is difficult to accrue such knowledge. Therefore, comparative research of these cancers in predisposed dog breeds, such as the Flatcoated retriever, can be of value. Histiocytic sarcoma in the dog can be grouped into a soft tissue- and visceral form. The soft tissue form at first is localized, while the visceral form progresses more quickly to a terminal state, which might be related to variations in gene expression. Microarray analyses were performed on fresh-frozen tissue from Flatcoated retrievers with either soft tissue- or visceral histiocytic sarcoma. Expression differences of ten most significantly differentially expressed genes were validated with quantitative real-time PCR (q PCR) analyses. Q PCR analyses confirmed the significantly aberrant expression of three of the selected genes: C6 was up-regulated; CLEC12A and CCL5 were down-regulated in the visceral histiocytic sarcoma compared to the soft tissue form. The findings of our study indicate that these two forms of histiocytic sarcoma in the dog display a variation in gene expression and warrant analysis of functional changes in the expression of those genes in these rare sarcomas in man.

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Section: Discussionsupporting

confidence: 85%

The Two Main Forms of Histiocytic Sarcoma in the Predisposed Flatcoated Retriever Dog Display Variation in Gene Expression

et al. 2014

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“…Invasive cells, like those which have undergone EMT, have been shown to be more sensitive to chemokine gradients (44,45). This may allow them to home to specific organs producing a chemoattractant (46,47), but it may also facilitate IFF-induced invasion, as we have outlined here.…”

Section: Discussionmentioning

confidence: 67%

EMT Transition Alters Interstitial Fluid Flow–Induced Signaling in ERBB2-Positive Breast Cancer Cells

Tchafa

Reginato

et al. 2015

Molecular Cancer Research

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A variety of biophysical forces are altered in the tumor microenvironment (TME) and these forces can influence cancer progression. One such force is interstitial fluid flow (IFF)-the movement of fluid through the tissue matrix. IFF was previously shown to induce invasion of cancer cells, but the activated signaling cascades remain poorly understood. Here, it is demonstrated that IFF induces invasion of ERBB2/HER2-expressing breast cancer cells via activation of phosphoinositide-3-kinase (PI3K). In constitutively activate ERBB2-expressing cells that have undergone epithelial-to-mesenchymal transition (EMT), IFF-mediated invasion requires the chemokine receptor CXCR4, a gradient of its ligand CXCL12, and activity of the PI3K catalytic subunits p110a and b. In wild-type ERBB2-expressing cells, IFF-mediated invasion is chemokine receptorindependent and requires only p110a activation. To test whether cells undergoing EMT alter their signaling response to IFF, TGFb1 was used to induce EMT in wild-type ERBB2-expressing cells, resulting in IFF-induced invasion dependent on CXCR4 and p110b.Implications: This study identifies a novel signaling mechanism for interstitial flow-induced invasion of ERBB2-expressing breast cancer cells, one that depends on EMT and acts through a CXCR4-PI3K pathway. These findings suggest that the response of cancer cells to interstitial flow depends on EMT status and malignancy.

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“…CCL5 is not only highly expressed by BCCs at the primary tumor and metastatic sites [26,27] but also expressed by stromal and immune cells, such as BMSCs, tumor-associated macrophages [28] , myeloid-derived suppressor cells, and T-regulatory cells [29] , in the tumor microenvironment. BCCs stimulate CCL5 secretion by BMSCs or other cells, and then CCL5 acts by binding with the highest affinity to CCR5 in BCCs to enhance their motility, invasion, and metastasis to distant organs [24,30] .…”

Section: Discussionmentioning

confidence: 99%

Wenshen Zhuanggu formula effectively suppresses breast cancer bone metastases in a mouse Xenograft model

Chen

Wang

et al. 2017

Acta Pharmacol Sin

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Wenshen Zhuanggu formula (WSZG) is a traditional Chinese medicine used as an adjuvant for the prevention of bone metastases in breast cancer patients. In this study we investigated the efficacy of WSZG in preventing bone metastases and the potential mechanisms in a mouse xenograft model of breast cancer bone metastases. This model was established by injection of human MDA-MB-231BO-Luc breast cancer cells alone or a mixture of the cancer cells with bone marrow-derived mesenchymal stem cells (BMSCs) into left ventricle of the heart in female nude mice. Then the mice were treated with WSZG (3.25, 6.5 or 13.0 mg·kg -1 ·d -1, ig) for four weeks, whereas zoledronic acid (100 µg/kg per week, ig) was used as a positive control. The occurrence and development of bone metastases were monitored via bioluminescent imaging, and bone lesions were assessed using micro-CT. Intracardiac injection of the mixture of MDA-MB-231BO-Luc breast cancer cells with BMSCs significantly facilitated the bone metastatic capacity of the breast cancer cells, and aggravated bone lesions in the mouse xenograft model of breast cancer bone metastases. Administration of WSZG dose-dependently inhibited the incidence and intensity of bone metastases and protected against bone lesions by suppressing osteoclast formation and tumor cell infiltration. Furthermore, administration of WSZG caused a marked reduction in the expression of CCL5/CCR5 and IL-17B/IL-17BR in bone metastatic tissues. The results demonstrate that WSZG exerts potential therapeutic effects in a mouse xenograft model of breast cancer bone metastases, which are partially mediated by weakening the interaction between BMSCs and breast cancer cells in the tumor microenvironment.

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Mesenchymal stem cell-derived CCL-9 and CCL-5 promote mammary tumor cell invasion and the activation of matrix metalloproteinases

Cited by 65 publications

References 60 publications

The Two Main Forms of Histiocytic Sarcoma in the Predisposed Flatcoated Retriever Dog Display Variation in Gene Expression

The Two Main Forms of Histiocytic Sarcoma in the Predisposed Flatcoated Retriever Dog Display Variation in Gene Expression

EMT Transition Alters Interstitial Fluid Flow–Induced Signaling in ERBB2-Positive Breast Cancer Cells

Wenshen Zhuanggu formula effectively suppresses breast cancer bone metastases in a mouse Xenograft model

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