Quantification of STAT3 and VEGF expression for molecular diagnosis of lymph node metastasis in breast cancer

Chen, Yujuan; Liu, Ya; Wang, Yu; Li, Wen; Wang, Xiaolu; Liu, Xuejuan; Yao, Chen; Ouyang, Chibin; Wang, Jing

doi:10.1097/md.0000000000008488

Cited by 12 publications

(6 citation statements)

References 21 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Seems clear the ability to improve the tumor spread by the lymph nodes microenvironment, which reinforce the importance of its removal along with that of the tumor, is a way to avoid its local or distant recurrence. Our finding is also in accordance with literature that postulate that cancer cells infiltrated in lymph nodes and surrounding macrophages as well, continues to produce VEGFs ligand and receptors molecules even in metastatic field, which enhance the aggressiveness of the tumors and their potential of continuing dissemination of malignant cells [29,30].…”

Section: Discussionsupporting

confidence: 93%

VEGF Expression in Colorectal Cancer Metastatic Lymph Nodes: Clinicopathological Correlation and Prognostic Significance

Mazeda

Martins

García

et al. 2020

Gastrointestinal Disorders

View full text Add to dashboard Cite

Background: Angiogenesis plays an important role in colorectal cancer (CRC) tumorigenesis and metastatic progression. Methods: The present series consisted of CRC lymph node metastasis (LNM) tissue samples from 210 patients. Archival paraffin embedded LNM tissue were used to build up tissue microarray blocks and VEGF expression was immunohistochemically assessed. Results: VEGF-A and VEGF-C are overexpressed in LNM. VEGF-A was associated with patient age (p < 0.001), and VEGFR-2 and VEGFR-3 with CRC relapse (p = 0.032; p = 0.030, respectively). VEGF-C positivity was associated with VEGFR-3 positivity (p = 0.031), and VEGF-D with VEGFR-2 and VEGFR-3 (p ≤ 0.001). Matching the expression in LNM with CRC, in CRC VEGF-A positivity associates with VEGF-A, VEGF-C, VEGF-D, VEGF-R2, VEGF-R3 positivity in LNM; CRC VEGF-C with VEGF-D, VEGFR-2, VEGFR-3; CRC VEGFR-2 with VEGF-A, VEGF-C, VEGF-D, VEGFR-2, VEGFR-3; CRC VEGFR-3 with VEGF-A, VEGF-C, VEGF-D, VEGFR-2, VEGFR-3 in LNM. Conclusion: This study provides new information, revealing that VEGF family expression is increased in LNM. The association between the expression of VEGFR-2 and VEGFR-3 in LNM with CRC relapse reveals its impact on patient prognosis. Interesting data were found when the relationship between these proteins in primary tumor and their metastasis, were analyzed; VEGFA positivity in primary tumor is positively related to VEGF-A, VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in their respective LNM suggesting mutual influence.

show abstract

Section: Discussionsupporting

confidence: 93%

VEGF Expression in Colorectal Cancer Metastatic Lymph Nodes: Clinicopathological Correlation and Prognostic Significance

Mazeda

Martins

García

et al. 2020

Gastrointestinal Disorders

View full text Add to dashboard Cite

show abstract

“…In the present study, VEGF expression was higher in NSCLC tumors compared with the tumor-adjacent normal tissues, and CCL25 treatment upregulated the expression of VEGF-C and -D in lung cancer cell lines, which could be blocked by the anti-CCR9 antibody. The aforementioned results were consistent with previous cancer-related studies on VEGF (47,48).…”

Section: Discussionsupporting

confidence: 93%

CCL25 promotes the migration and invasion of non‑small cell lung cancer cells by regulating VEGF and MMPs in a CCR9‑dependent manner

et al. 2020

View full text Add to dashboard Cite

The CC chemokine receptor 9 (CCR9) and its natural secreted ligand CC motif chemokine ligand 25 (CCL25) have been implicated in cancer metastasis. However, their metastatic potential in non-small cell lung cancer (NSCLC) remains unclear. In the present study, immunohistochemistry was used to detect the expression and localization of CCR9, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and MMP-7 in lung cancer tissue and adjacent normal tissue. The association between the expression of CCR9 and clinical variables was also examined. Reverse transcription-quantitative PCR and western blotting were conducted to detect the expression of VEGF-C, VEGF-D, MMP-1 and MMP-7 in lung cancer cell lines (A549 and SK-MES-1). Migration and invasion assays were conducted to examine cell migration and invasion. Survival and mutation analysis were conducted using published datasets. The expressions of CCR9, VEGF, MMP-1 and MMP-7 were upregulated in cancer tissue, compared with adjacent normal tissue (all P<0.05). Patients with lower expression of CCR9 or CCL25 had better overall survival (OS) compared with those with higher CCR9 or CCL25 expression (P<0.05 and P=0.05, respectively). Furthermore, the expressions of VEGF-C, VEGF-D, MMP-1 and MMP-7 were higher in the CCL25-treated cell lines (all P<0.05), but MMP-7 protein expression was not affected by CCL25 treatment in SK-MES-1 cells (P>0.05). Following treatment with CCL25, lung cancer cells demonstrated higher migratory and invasive potential, which could be blocked by the CCR9 antibody (P<0.05). Survival analysis demonstrated that low expression levels of both CCR9 and CCL25 mRNA indicated favorable OS in patients with NSCLC. Altogether, these results suggested that CCL25 enhanced the phenotype associated with migration and invasion in NSCLC by regulating the expression of VEGF-C, VEGF-D, MMP-1 and MMP-7.

show abstract

“…Our group and others previously demonstrated that STAT3 is an essential mediator of endothelial activation by directly inducing VEGF and HIF1a gene expression ( 116 , 117 ). On a functional level, STAT3 signaling has been reported to promote angiogenesis in human pancreatic, lung, and breast cancers ( 118 – 120 ) and we have previously shown that STAT3 is a critical regulator of the pro-angiogenic functions of myeloid cells in mice ( 121 ). In ovarian cancers, the expression of VEGF and its receptors VEGFR1 and VEGFR2 significantly correlate with pSTAT3 levels in patient samples ( 122 ), and STAT3 and VEGF have been shown to reciprocally regulate each other’s expression and activation in EOC models ( 123 , 124 ).…”

Section: Cd44 and Stat3 In Ovarian Tumor Microenvironmentmentioning

confidence: 96%

CD44 in Ovarian Cancer Progression and Therapy Resistance—A Critical Role for STAT3

Martincuks

Zhao

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Despite significant progress in cancer therapy over the last decades, ovarian cancer remains the most lethal gynecologic malignancy worldwide with the five-year overall survival rate less than 30% due to frequent disease recurrence and chemoresistance. CD44 is a non-kinase transmembrane receptor that has been linked to cancer metastatic progression, cancer stem cell maintenance, and chemoresistance development via multiple mechanisms across many cancers, including ovarian, and represents a promising therapeutic target for ovarian cancer treatment. Moreover, CD44-mediated signaling interacts with other well-known pro-tumorigenic pathways and oncogenes during cancer development, such as signal transducer and activator of transcription 3 (STAT3). Given that both CD44 and STAT3 are strongly implicated in the metastatic progression and chemoresistance of ovarian tumors, this review summarizes currently available evidence about functional crosstalk between CD44 and STAT3 in human malignancies with an emphasis on ovarian cancer. In addition to the role of tumor cell-intrinsic CD44 and STAT3 interaction in driving cancer progression and metastasis, we discuss how CD44 and STAT3 support the pro-tumorigenic tumor microenvironment and promote tumor angiogenesis, immunosuppression, and cancer metabolic reprogramming in favor of cancer progression. Finally, we review the current state of therapeutic CD44 targeting and propose superior treatment possibilities for ovarian cancer.

show abstract

Quantification of STAT3 and VEGF expression for molecular diagnosis of lymph node metastasis in breast cancer

Cited by 12 publications

References 21 publications

VEGF Expression in Colorectal Cancer Metastatic Lymph Nodes: Clinicopathological Correlation and Prognostic Significance

VEGF Expression in Colorectal Cancer Metastatic Lymph Nodes: Clinicopathological Correlation and Prognostic Significance

CCL25 promotes the migration and invasion of non‑small cell lung cancer cells by regulating VEGF and MMPs in a CCR9‑dependent manner

CD44 in Ovarian Cancer Progression and Therapy Resistance—A Critical Role for STAT3

Contact Info

Product

Resources

About