Limits...
SDF-1alpha concentration dependent modulation of RhoA and Rac1 modifies breast cancer and stromal cells interaction.

Pasquier J, Abu-Kaoud N, Abdesselem H, Madani A, Hoarau-Véchot J, Thawadi HA, Vidal F, Couderc B, Favre G, Rafii A - BMC Cancer (2015)

Bottom Line: This interaction increases migration from primary sites as well as homing at distant sites.Increased migration was obtained at 50 and 100 ng/ml of SDF-1α; however migration was reduced at 200 ng/ml.The adhesion between breast cancer cells and BMHC was significantly increased by SDF-1α treatment at 200 ng/ml and reduced using a blocking monoclonal antibody against CXCR4.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar. jep2026@qatar-med.cornell.edu.

ABSTRACT

Background: The interaction of SDF-1alpha with its receptor CXCR4 plays a role in the occurrence of distant metastasis in many solid tumors. This interaction increases migration from primary sites as well as homing at distant sites.

Methods: Here we investigated how SDF-1α could modulate both migration and adhesion of cancer cells through the modulation of RhoGTPases.

Results: We show that different concentrations of SDF-1α modulate the balance of adhesion and migration in cancer cells. Increased migration was obtained at 50 and 100 ng/ml of SDF-1α; however migration was reduced at 200 ng/ml. The adhesion between breast cancer cells and BMHC was significantly increased by SDF-1α treatment at 200 ng/ml and reduced using a blocking monoclonal antibody against CXCR4. We showed that at low SDF-1α concentration, RhoA was activated and overexpressed, while at high concentration Rac1 was promoting SDF-1α mediating-cell adhesion.

Conclusion: We conclude that SDF-1α concentration modulates migration and adhesion of breast cancer cells, by controlling expression and activation of RhoGTPases.

No MeSH data available.


Related in: MedlinePlus

Differential role of small GTPase in BMHC and MDA-MB231 interactions
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4522077&req=5

Fig7: Differential role of small GTPase in BMHC and MDA-MB231 interactions

Mentions: Our understanding of metastatic development in breast cancer is crucial to design novel therapeutic strategies. The role of the microenvironmental cues, in particular the cytokine mediated signaling has been already established in breast cancer metastasis. Here using an in vitro approach we were able to explain two apparently contradictory roles of the interaction between SDF-1α/CXCR4. We showed that while low concentration of SDF-1α promoted cell migration through RhoA activation, high concentration of the cytokine promoted intercellular interaction through Rac1 activation (Fig. 7). Our findings shed light on the dynamics of the interaction between breast cancer cells and their microenvironment, as well as the dual role of SDF-1α.Fig. 7


SDF-1alpha concentration dependent modulation of RhoA and Rac1 modifies breast cancer and stromal cells interaction.

Pasquier J, Abu-Kaoud N, Abdesselem H, Madani A, Hoarau-Véchot J, Thawadi HA, Vidal F, Couderc B, Favre G, Rafii A - BMC Cancer (2015)

Differential role of small GTPase in BMHC and MDA-MB231 interactions
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522077&req=5

Fig7: Differential role of small GTPase in BMHC and MDA-MB231 interactions
Mentions: Our understanding of metastatic development in breast cancer is crucial to design novel therapeutic strategies. The role of the microenvironmental cues, in particular the cytokine mediated signaling has been already established in breast cancer metastasis. Here using an in vitro approach we were able to explain two apparently contradictory roles of the interaction between SDF-1α/CXCR4. We showed that while low concentration of SDF-1α promoted cell migration through RhoA activation, high concentration of the cytokine promoted intercellular interaction through Rac1 activation (Fig. 7). Our findings shed light on the dynamics of the interaction between breast cancer cells and their microenvironment, as well as the dual role of SDF-1α.Fig. 7

Bottom Line: This interaction increases migration from primary sites as well as homing at distant sites.Increased migration was obtained at 50 and 100 ng/ml of SDF-1α; however migration was reduced at 200 ng/ml.The adhesion between breast cancer cells and BMHC was significantly increased by SDF-1α treatment at 200 ng/ml and reduced using a blocking monoclonal antibody against CXCR4.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar. jep2026@qatar-med.cornell.edu.

ABSTRACT

Background: The interaction of SDF-1alpha with its receptor CXCR4 plays a role in the occurrence of distant metastasis in many solid tumors. This interaction increases migration from primary sites as well as homing at distant sites.

Methods: Here we investigated how SDF-1α could modulate both migration and adhesion of cancer cells through the modulation of RhoGTPases.

Results: We show that different concentrations of SDF-1α modulate the balance of adhesion and migration in cancer cells. Increased migration was obtained at 50 and 100 ng/ml of SDF-1α; however migration was reduced at 200 ng/ml. The adhesion between breast cancer cells and BMHC was significantly increased by SDF-1α treatment at 200 ng/ml and reduced using a blocking monoclonal antibody against CXCR4. We showed that at low SDF-1α concentration, RhoA was activated and overexpressed, while at high concentration Rac1 was promoting SDF-1α mediating-cell adhesion.

Conclusion: We conclude that SDF-1α concentration modulates migration and adhesion of breast cancer cells, by controlling expression and activation of RhoGTPases.

No MeSH data available.


Related in: MedlinePlus