The Signaling Duo CXCL12 and CXCR4: Chemokine Fuel for Breast Cancer Tumorigenesis

Zielińska, Karolina; Katanaev, Vladimir L.

doi:10.3390/cancers12103071

Cited by 49 publications

(71 citation statements)

References 152 publications

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“…The role of chemokines and chemokine receptors has gained increasing attention over the past 20 years, and CXCL12 is one of the most studied [ 78 ]. Mediating its effects by binding to its major corresponding receptor, CXCR4, CXCL12 is implicated in inflammatory responses, autoimmune diseases, T cell homing, angiogenesis, CAFs activation, EMT, tumor progression, metastasis, and therapy resistance [ 199 , 200 , 201 , 202 ]. A high expression and activation of the CXCL12/CXCR4 axis can be found at preferred metastatic sites such as lymph nodes, liver, lungs, and the bone marrow associated with poor prognosis [ 195 , 203 , 204 , 205 ].…”

Section: Impact Of Inflammation On Cancer Metastases To Bonementioning

confidence: 99%

The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone

Göbel

Dell'Endice

Jaschke

et al. 2021

IJMS

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Tumor metastasis to bone is a common event in multiple forms of malignancy. Inflammation holds essential functions in homeostasis as a defense mechanism against infections and is a strategy to repair injured tissue and to adapt to stress conditions. However, exaggerated and/or persistent (chronic) inflammation may eventually become maladaptive and evoke diseases such as autoimmunity, diabetes, inflammatory tissue damage, fibrosis, and cancer. In fact, inflammation is now considered a hallmark of malignancy with prognostic relevance. Emerging studies have revealed a central involvement of inflammation in several steps of the metastatic cascade of bone-homing tumor cells through supporting their survival, migration, invasion, and growth. The mechanisms by which inflammation favors these steps involve activation of epithelial-to-mesenchymal transition (EMT), chemokine-mediated homing of tumor cells, local activation of osteoclastogenesis, and a positive feedback amplification of the protumorigenic inflammation loop between tumor and resident cells. In this review, we summarize established and evolving concepts of inflammation-driven tumorigenesis, with a special focus on bone metastasis.

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Section: Impact Of Inflammation On Cancer Metastases To Bonementioning

confidence: 99%

The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone

Göbel

Dell'Endice

Jaschke

et al. 2021

IJMS

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“…In the context of breast cancer cell dissemination, this signaling appears to work via CXCR4 on the tumor cells, underscoring local hypoxic signaling in the BM niche exerting control on distant tumors, impacting growth and metastasis ( Xu et al, 2015 ). This suggests that targeting CXCL12/CXCR4 would be beneficial, but different experimental approaches reveal case-by-case differences ( Zielinska and Katanaev, 2020 ). Indeed, although systemic CXCR4 inhibition might be beneficial in breast cancer growth, deficiency of CXCR4 in osteoclasts was shown to enhance osteoclastogenesis, which in turn may again promote bone metastasis and stimulate the vicious cycle ( Zielinska and Katanaev, 2020 ).…”

Section: Role Of Hypoxia In the Regulation Of Osteoclasts In Osteolytmentioning

confidence: 99%

“…This suggests that targeting CXCL12/CXCR4 would be beneficial, but different experimental approaches reveal case-by-case differences ( Zielinska and Katanaev, 2020 ). Indeed, although systemic CXCR4 inhibition might be beneficial in breast cancer growth, deficiency of CXCR4 in osteoclasts was shown to enhance osteoclastogenesis, which in turn may again promote bone metastasis and stimulate the vicious cycle ( Zielinska and Katanaev, 2020 ).…”

Section: Role Of Hypoxia In the Regulation Of Osteoclasts In Osteolytmentioning

confidence: 99%

Hypoxia-Inducible Factors Regulate Osteoclasts in Health and Disease

Meng

Wielockx

Rauner

et al. 2021

Front. Cell Dev. Biol.

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Hypoxia-inducible factors (HIFs) have become key transcriptional regulators of metabolism, angiogenesis, erythropoiesis, proliferation, inflammation and metastases. HIFs are tightly regulated by the tissue microenvironment. Under the influence of the hypoxic milieu, HIF proteins allow the tissue to adapt its response. This is especially critical for bone, as it constitutes a highly hypoxic environment. As such, bone structure and turnover are strongly influenced by the modulation of oxygen availability and HIFs. Both, bone forming osteoblasts and bone resorbing osteoclasts are targeted by HIFs and modulators of oxygen tension. Experimental and clinical data have delineated the importance of HIF responses in different osteoclast-mediated pathologies. This review will focus on the influence of HIF expression on the regulation of osteoclasts in homeostasis as well as during inflammatory and malignant bone diseases.

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“…Breast cancer is the most common cancer in women worldwide, and early diagnosis of breast cancer can be curable in 70-80% of patients [10]. However, the development of metastatic breast cancer is poor prognosis and accounts for over 90% of breast cancerrelated mortality [11].…”

Section: Introductionmentioning

confidence: 99%

Rhosin Suppressed Tumor Cell Metastasis through Inhibition of Rho/YAP Pathway and Expression of RHAMM and CXCR4 in Melanoma and Breast Cancer Cells

et al. 2021

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The high mortality rate of cancer is strongly correlated with the development of distant metastases at secondary sites. Although Rho GTPases, such as RhoA, RhoB, RhoC, and RhoE, promote tumor metastasis, the main roles of Rho GTPases remain unidentified. It is also unclear whether rhosin, a Rho inhibitor, acts by suppressing metastasis by a downstream inhibition of Rho. In this study, we investigated this mechanism of metastasis in highly metastatic melanoma and breast cancer cells, and the mechanism of inhibition of metastasis by rhosin. We found that rhosin suppressed the RhoA and RhoC activation, the nuclear localization of YAP, but did not affect ERK1/2, Akt, or NF-κB activation in the highly metastatic cell lines B16BL6 and 4T1. High expression of YAP was associated with poor overall and recurrence-free survival in patients with breast cancer or melanoma. Treatment with rhosin inhibited lung metastasis in vivo. Moreover, rhosin inhibited tumor cell adhesion to the extracellular matrix via suppression of RHAMM expression, and inhibited SDF-1-induced cell migration and invasion by decreasing CXCR4 expression in B16BL6 and 4T1 cells. These results suggest that the inhibition of RhoA/C-YAP pathway by rhosin could be an extremely useful therapeutic approach in patients with melanoma and breast cancer.

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The Signaling Duo CXCL12 and CXCR4: Chemokine Fuel for Breast Cancer Tumorigenesis

Cited by 49 publications

References 152 publications

The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone

The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone

Hypoxia-Inducible Factors Regulate Osteoclasts in Health and Disease

Rhosin Suppressed Tumor Cell Metastasis through Inhibition of Rho/YAP Pathway and Expression of RHAMM and CXCR4 in Melanoma and Breast Cancer Cells

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