Prognostic significance of SDF-1 chemokine and its receptors CXCR4 and CXCR7 involved in EMT of prostate cancer

Parol-Kulczyk, Martyna; Gzil, Arkadiusz; Ligmanowska, Joanna; Grzanka, Dariusz

doi:10.1016/j.cyto.2021.155778

Cited by 13 publications

(9 citation statements)

References 71 publications

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“…To determine whether the identified MAOB-CXCL12 axis in stromal cells could be recapitulated in the clinical setting, we assessed MAOB and CXCL12 protein levels in serial sections of a human PC TMA by IHC. Consistent with previous reports ( 69 , 70 ) and our findings above (fig. S1), MAOB and CXCL12 were found to be expressed in both tumor and stromal cells.…”

Section: Resultssupporting

confidence: 94%

Stromal-derived MAOB promotes prostate cancer growth and progression

Pu,

Wang,

Wei

et al. 2024

Sci. Adv.

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Prostate cancer (PC) develops in a microenvironment where the stromal cells modulate adjacent tumor growth and progression. Here, we demonstrated elevated levels of monoamine oxidase B (MAOB), a mitochondrial enzyme that degrades biogenic and dietary monoamines, in human PC stroma, which was associated with poor clinical outcomes of PC patients. Knockdown or overexpression of MAOB in human prostate stromal fibroblasts indicated that MAOB promotes cocultured PC cell proliferation, migration, and invasion and co-inoculated prostate tumor growth in mice. Mechanistically, MAOB induces a reactive stroma with activated marker expression, increased extracellular matrix remodeling, and acquisition of a protumorigenic phenotype through enhanced production of reactive oxygen species. Moreover, MAOB transcriptionally activates CXCL12 through Twist1 synergizing with TGFβ1-dependent Smads in prostate stroma, which stimulates tumor-expressed CXCR4-Src/JNK signaling in a paracrine manner. Pharmacological inhibition of stromal MAOB restricted PC xenograft growth in mice. Collectively, these findings characterize the contribution of MAOB to PC and suggest MAOB as a potential stroma-based therapeutic target.

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Section: Resultssupporting

confidence: 94%

Stromal-derived MAOB promotes prostate cancer growth and progression

Pu,

Wang,

Wei

et al. 2024

Sci. Adv.

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“…Interestingly, from a set of stromal markers (PDGFRβ, SMA, and SDF1) previously related to primary tumor aggressiveness [ 15 , 22 , 23 , 24 ], none appeared to be associated with patient prognosis after ADT in this patient cohort. Furthermore, they were also not predictive of the metastasis subtypes.…”

Section: Discussionmentioning

confidence: 82%

Epithelial and Stromal Characteristics of Primary Tumors Predict the Bone Metastatic Subtype of Prostate Cancer and Patient Survival after Androgen-Deprivation Therapy

Wikström

Bergström

Josefsson

et al. 2022

Cancers

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Prostate cancer (PC) bone metastases can be divided into transcriptomic subtypes, by us termed MetA-C. The MetB subtype, constituting about 20% of the cases, is characterized by high cell cycle activity, low androgen receptor (AR) activity, and a limited response to standard androgen deprivation therapy (ADT). Complementary treatments should preferably be introduced early on if the risk of developing metastases of the MetB subtype is predicted to behigh. In this study, we therefore examined if the bone metastatic subtype and patient outcome after ADT could be predicted by immunohistochemical analysis of epithelial and stromal cell markers in primary tumor biopsies obtained at diagnosis (n = 98). In this advanced patient group, primary tumor International Society of Urological Pathology (ISUP) grade was not associated with outcome or metastasis subtype. In contrast, high tumor cell Ki67 labeling (proliferation) in combination with low tumor cell immunoreactivity for PSA, and a low fraction of AR positive stroma cells in the primary tumors were prognostic for poor survival after ADT. Accordingly, the same tissue markers were associated with developing metastases enriched for the aggressive MetB subtype. The development of the contrasting MetA subtype, showing the best response to ADT, could be predicted by the opposite staining pattern. We conclude that outcome after ADT and metastasis subtype can, at least to some extent, be predicted by analysis of primary tumor characteristics, such as tumor cell proliferation and PSA expression, and AR expression in stromal cells.

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“…SDF-1 activates downstream signaling pathways, such as PAM and ERK1/2, and enhances cancer cell survival, proliferation, and chemotaxis by binding to its receptor CXCR4 ( 23 ). Previous studies have shown that high expression of SDF-1/CXCR4 is correlated with poor survival in various tumors, such as colorectal cancer ( 24 ), prostate cancer ( 25 ), pancreatic cancer ( 26 ), and breast cancer ( 27 ). However, limited data have reported the value of SDF-1/CXCR4 in predicting chemotherapy response.…”

Section: Discussionmentioning

confidence: 99%

SDF-1 expression and tumor-infiltrating lymphocytes identify clinical subtypes of triple-negative breast cancer with different responses to neoadjuvant chemotherapy and survival

Wang

Ji²,

Gong³

et al. 2022

Front. Immunol.

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BackgroundIn this study, we investigated the prediction and prognostic value of SDF-1 for triple-negative breast cancer (TNBC) patients who underwent neoadjuvant chemotherapy (NAC) following standard radical surgery.MethodsA total of 303 TNBC patients were included in this study. The NAC regimen was weekly paclitaxel plus carboplatin (PC) for all patients. SDF-1 and CXCR4 expression were measured at baseline and surgery via enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively. Correlations between variables and treatment response were studied, and Cox proportional hazards regression analysis was implemented for prognostic evaluation.ResultsOf the 303 patients, 103 (34.0%) experienced pathological complete response (pCR) after completion of NAC. Serum SDF-1 expression before NAC was significantly correlated with the abundance of TILs. A higher pCR rate was more likely to be observed in patients with lower serum SDF-1 levels before NAC (P=0.001, OR=0.997, 95% CI: 0.996-0.999) and higher levels of TILs (P=0.005). In the multivariate survival model for nonpCR patients, serum SDF-1 expression at surgery served as an independent prognostic value for survival (high level, HR=1.980, 95% CI: 1.170-3.350, low level was used as a reference; P=0.011). Additionally, the predictive and prognostic value of serum SDF-1 expression was significant in patients with high abundance of TILs but not in patients with low abundance of TILs.ConclusionsThis study contributes to the clarification of the value of serum SDF-1 to predict pCR and survival for TNBC patients who underwent NAC. This new serum marker, together with TILs, might help identify clinical subtypes of TNBC with different treatment responses and survival and play an important role in tailoring and modifying the NAC strategy for advanced TNBCs in the future.

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Prognostic significance of SDF-1 chemokine and its receptors CXCR4 and CXCR7 involved in EMT of prostate cancer

Cited by 13 publications

References 71 publications

Stromal-derived MAOB promotes prostate cancer growth and progression

Stromal-derived MAOB promotes prostate cancer growth and progression

Epithelial and Stromal Characteristics of Primary Tumors Predict the Bone Metastatic Subtype of Prostate Cancer and Patient Survival after Androgen-Deprivation Therapy

SDF-1 expression and tumor-infiltrating lymphocytes identify clinical subtypes of triple-negative breast cancer with different responses to neoadjuvant chemotherapy and survival

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