CXCR7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors

Mashael Al-Toub, Mohammad Almohawes, Radhakrishnan Vishnubalaji, Musaad Alfayez, Abdullah Aldahmash, Moustapha Kassem, Nehad M Alajez

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Resumé

The interaction between cancer cells and molecular cues provided by tumor stromal cells plays a crucial role in cancer growth and progression. We have recently reported that the outcome of interaction between tumor cells and stromal cells is dependent on the gene expression signature of tumor cells. In the current study, we observed that several cancer cell lines, e.g., MCF7 breast cancer line, exhibited growth advantage when cultured in the presence of conditioned media (CM) derived from human bone marrow stromal stem cells (hBMSCs). Regarding the underlying molecular mechanism, we have identified CXCR7 as highly expressed by MCF7 cells and that it mediated the enhanced growth in response to hBMSC CM. Regarding the clinical relevance, we found an inverse correlation between the level of tumor gene expression of CXCR7 in bladder, breast, cervical, kidney, liver, lung, pancreatic, stomach, and uterine cancers, and patients' overall survival. Interestingly, significant positive correlation between CXCR7 and CXCL12 gene expression (Pearson = 0.3, p = 2.0 × 10-16) was observed in breast cancer patients, suggesting a biological role for the CXCR7/CXCL12 genetic circuit in breast cancer biology. Our data provide insight into the molecular mechanisms by which stromal-derived microenvironmental cues mediate CXCR7 signaling and growth enhancement of breast cancer cells. Therapeutic targeting of this circuit might provide novel therapeutic opportunity for breast cancer.

OriginalsprogEngelsk
Artikelnummer87
TidsskriftCell Death Discovery
Vol/bind5
Antal sider9
ISSN2058-7716
DOI
StatusUdgivet - 2019

Fingeraftryk

Stem Cell Factor
Mesenchymal Stromal Cells
Neoplasms
Stromal Cells
Conditioned Culture Medium
Growth
Cues
Uterine Neoplasms
Kidney Neoplasms
MCF-7 Cells
Liver Neoplasms
Pancreatic Neoplasms
Transcriptome
Uterine Cervical Neoplasms
Cell Line

Citer dette

Al-Toub, Mashael ; Almohawes, Mohammad ; Vishnubalaji, Radhakrishnan ; Alfayez, Musaad ; Aldahmash, Abdullah ; Kassem, Moustapha ; Alajez, Nehad M. / CXCR7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors. I: Cell Death Discovery. 2019 ; Bind 5.
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title = "CXCR7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors",
abstract = "The interaction between cancer cells and molecular cues provided by tumor stromal cells plays a crucial role in cancer growth and progression. We have recently reported that the outcome of interaction between tumor cells and stromal cells is dependent on the gene expression signature of tumor cells. In the current study, we observed that several cancer cell lines, e.g., MCF7 breast cancer line, exhibited growth advantage when cultured in the presence of conditioned media (CM) derived from human bone marrow stromal stem cells (hBMSCs). Regarding the underlying molecular mechanism, we have identified CXCR7 as highly expressed by MCF7 cells and that it mediated the enhanced growth in response to hBMSC CM. Regarding the clinical relevance, we found an inverse correlation between the level of tumor gene expression of CXCR7 in bladder, breast, cervical, kidney, liver, lung, pancreatic, stomach, and uterine cancers, and patients' overall survival. Interestingly, significant positive correlation between CXCR7 and CXCL12 gene expression (Pearson = 0.3, p = 2.0 × 10-16) was observed in breast cancer patients, suggesting a biological role for the CXCR7/CXCL12 genetic circuit in breast cancer biology. Our data provide insight into the molecular mechanisms by which stromal-derived microenvironmental cues mediate CXCR7 signaling and growth enhancement of breast cancer cells. Therapeutic targeting of this circuit might provide novel therapeutic opportunity for breast cancer.",
author = "Mashael Al-Toub and Mohammad Almohawes and Radhakrishnan Vishnubalaji and Musaad Alfayez and Abdullah Aldahmash and Moustapha Kassem and Alajez, {Nehad M}",
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CXCR7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors. / Al-Toub, Mashael; Almohawes, Mohammad; Vishnubalaji, Radhakrishnan; Alfayez, Musaad; Aldahmash, Abdullah; Kassem, Moustapha; Alajez, Nehad M.

I: Cell Death Discovery, Bind 5, 87, 2019.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - CXCR7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors

AU - Al-Toub, Mashael

AU - Almohawes, Mohammad

AU - Vishnubalaji, Radhakrishnan

AU - Alfayez, Musaad

AU - Aldahmash, Abdullah

AU - Kassem, Moustapha

AU - Alajez, Nehad M

PY - 2019

Y1 - 2019

N2 - The interaction between cancer cells and molecular cues provided by tumor stromal cells plays a crucial role in cancer growth and progression. We have recently reported that the outcome of interaction between tumor cells and stromal cells is dependent on the gene expression signature of tumor cells. In the current study, we observed that several cancer cell lines, e.g., MCF7 breast cancer line, exhibited growth advantage when cultured in the presence of conditioned media (CM) derived from human bone marrow stromal stem cells (hBMSCs). Regarding the underlying molecular mechanism, we have identified CXCR7 as highly expressed by MCF7 cells and that it mediated the enhanced growth in response to hBMSC CM. Regarding the clinical relevance, we found an inverse correlation between the level of tumor gene expression of CXCR7 in bladder, breast, cervical, kidney, liver, lung, pancreatic, stomach, and uterine cancers, and patients' overall survival. Interestingly, significant positive correlation between CXCR7 and CXCL12 gene expression (Pearson = 0.3, p = 2.0 × 10-16) was observed in breast cancer patients, suggesting a biological role for the CXCR7/CXCL12 genetic circuit in breast cancer biology. Our data provide insight into the molecular mechanisms by which stromal-derived microenvironmental cues mediate CXCR7 signaling and growth enhancement of breast cancer cells. Therapeutic targeting of this circuit might provide novel therapeutic opportunity for breast cancer.

AB - The interaction between cancer cells and molecular cues provided by tumor stromal cells plays a crucial role in cancer growth and progression. We have recently reported that the outcome of interaction between tumor cells and stromal cells is dependent on the gene expression signature of tumor cells. In the current study, we observed that several cancer cell lines, e.g., MCF7 breast cancer line, exhibited growth advantage when cultured in the presence of conditioned media (CM) derived from human bone marrow stromal stem cells (hBMSCs). Regarding the underlying molecular mechanism, we have identified CXCR7 as highly expressed by MCF7 cells and that it mediated the enhanced growth in response to hBMSC CM. Regarding the clinical relevance, we found an inverse correlation between the level of tumor gene expression of CXCR7 in bladder, breast, cervical, kidney, liver, lung, pancreatic, stomach, and uterine cancers, and patients' overall survival. Interestingly, significant positive correlation between CXCR7 and CXCL12 gene expression (Pearson = 0.3, p = 2.0 × 10-16) was observed in breast cancer patients, suggesting a biological role for the CXCR7/CXCL12 genetic circuit in breast cancer biology. Our data provide insight into the molecular mechanisms by which stromal-derived microenvironmental cues mediate CXCR7 signaling and growth enhancement of breast cancer cells. Therapeutic targeting of this circuit might provide novel therapeutic opportunity for breast cancer.

U2 - 10.1038/s41420-019-0169-3

DO - 10.1038/s41420-019-0169-3

M3 - Journal article

C2 - 30993013

VL - 5

JO - Cell Death Discovery

JF - Cell Death Discovery

SN - 2058-7716

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ER -