Distinct prognostic values of S100 mRNA expression in breast cancer

Zhang, Shizhen; Wang, Zhen; Liu, Weiwei; Li, Rui; Shan, Jixiu; Li, Ling; Wang, Xiaochen

doi:10.1038/srep39786

Cited by 72 publications

(65 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We saw a significant increase in CSF-2 expression in PyMT/p11-KO tumors but CSF-2 has not been shown to correlate with macrophage infiltration in breast tumors. We also observed a Previous gene expression studies showed that p11 correlated to poor overall survival in basal-like breast cancer (reviewed in (57). In elucidating the prognostic role of p11 in human breast cancer, we found that p11 mRNA was overexpressed in human breast tumors, correlated positively with overall survival and recurrence-free survival, and was increased in high grade tumors compared to low grade tumors and normal tissue.…”

Section: Discussionsupporting

confidence: 63%

S100A10 has a Critical Regulatory Function in Mammary Tumor Growth and Metastasis: Insights using MMTV-PyMT Oncomice and Clinical Patient Sample Analysis.

Bharadwaj

Dahn

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Breast cancer is one of the leading causes of cancer deaths in women worldwide. Significant advances have been made in the diagnosis and treatment of breast cancer, treatment of triple-negative and metastatic breast cancer poses significant challenge. Metastasis is a multi-step cascade that involves activation of proteases such as plasmin to facilitate the invasive escape of tumor cells to distant organs. The rate-limiting step in plasmin generation requires the interaction of plasminogen with cell surface plasminogen binding sites. Our laboratory first demonstrated that the plasminogen receptor, S100A10 (p11) was upregulated in many cancer cells and was responsible for much of their plasmin generation. Recently, it was reported that p11 is one of a few genes that are activated when human breast cancer cells metastasize from the primary tumor into the blood and is upregulated during the conversion of breast cancer cells to invasive phenotype. In the current study we have investigated the role of p11 in breast cancer tumor progression.Methods: We have used MMTV-PyMT a mouse transgenic mammary tumor model to investigate the effects of loss of p11 on spontaneous tumor initiation, growth and progression to invasive carcinoma and metastasis. We used experimental metastasis assays to ascertain the role of stromal p11 in tumor cell extravasation and lung colonization. Genes and cytokines regulated by p11 in the PyMT tumors were assessed by microarray analysis and RT-qPCR. Finally, we employed gene profiling analysis and immunohistochemical staining of breast cancer patient tumors to correlate p11 expression to human breast cancer progression. Results: Genetic deletion of p11 resulted in significantly decreased tumor onset, growth rate, and spontaneous pulmonary metastatic burden in the PyMT/p11-KO mice. This phenotype was accompanied by substantial reduction in Ki67 positivity, macrophage infiltration, decreased vascular density in the primary tumors and decrease in invasive carcinoma and pulmonary metastasis. Surprisingly, immunohistochemical analysis of wild-type MMTV-PyMT mice failed to detect p11 expression in the tumors or metastatic tumor cells and loss of p11 did not decrease plasmin generation in the PyMT tumors and cells. Furthermore, tumor cells expressing p11 displayed dramatically reduced lung metastasis when injected into p11-depleted mice, further strengthening the stromal role of p11 in tumor growth and metastasis. Transcriptome analysis of the PyMT tumors from p11-KO mice showed marked reduction in genes involved in breast cancer development, progression, and inflammation such as AREG, MUC1 and S100A8. The PyMT/p11- KO tumors displayed a remarkable increase in inflammatory cytokines such as IL-6, IL-10 and IFN-γ. Gene expression profiling from 176 primary breast cancer samples obtained through the CBCF tumor bank showed that p11 mRNA levels were significantly higher in tumors compared to normal tissues. P11 mRNA expression was significantly associated with poor patient prognosis (hazard ratio – 3.34) and significantly elevated in high grade, triple negative (TN) tumors, and tumors with high proliferative index. Evaluation of p11 protein expression in a NSHA cohort of patients revealed substantial upregulation of p11 in cancer tissues compared to normal controls. Conclusions: This is the first study demonstrating the crucial role of p11 in breast tumor development and metastasis. The results emphasize the potential of p11 as a diagnostic and prognostic biomarker in breast cancer.

show abstract

Section: Discussionsupporting

confidence: 63%

S100A10 has a Critical Regulatory Function in Mammary Tumor Growth and Metastasis: Insights using MMTV-PyMT Oncomice and Clinical Patient Sample Analysis.

Bharadwaj

Dahn

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…S100A6 expression has been associated with worse prognosis or the progression of several cancers including oncogynecology [50], colorectal [51], gastric [52], and renal [53]. In contrast, a recent study suggests a relation between S100A6 expression and better prognosis in breast cancer [54]. However, to the best of our knowledge, this is the first report in which the S100A family is described in saliva of bitches with mammary tumors.…”

Section: Discussionmentioning

confidence: 97%

Changes in Serum and Salivary Proteins in Canine Mammary Tumors

Franco‐Martínez

Gelemanović

Horvatić

et al. 2020

Animals

View full text Add to dashboard Cite

The aim of this study was to evaluate changes in serum and saliva proteomes in canine mammary tumors (CMT) using a high-throughput quantitative proteomic analysis in order to potentially discover possible biomarkers of this disease. Proteomes of paired serum and saliva samples from healthy controls (HC group, n = 5) and bitches with CMT (CMT group, n = 5) were analysed using a Tandem Mass Tags-based approach. Twenty-five dogs were used to validate serum albumin as a candidate biomarker in an independent sample set. The proteomic analysis quantified 379 and 730 proteins in serum and saliva, respectively. Of those, 35 proteins in serum and 49 in saliva were differentially represented. The verification of albumin in serum was in concordance with the proteomic data, showing lower levels in CMT when compared to the HC group. Some of the modulated proteins found in the present study such as haptoglobin or S100A4 have been related to CMT or human breast cancer previously, while others such as kallikrein-1 and immunoglobulin gamma-heavy chains A and D are described here for the first time. Our results indicate that saliva and serum proteomes can reflect physiopathological changes that occur in CMT in dogs and can be a potential source of biomarkers of the disease.

show abstract

“…It is additionally interesting to note that 14/18 of the upregulated protein-validated factors are associated with poor prognosis or invasion in breast cancers, when measured in serum or tissue; this suggests that cells which secrete these factors would have a negative impact on prognosis 39,41,47,49,54,[56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72] . It is also of interest to note that in these studies 8/14 of these poorly prognostic factors have been seen to derive predominantly from stromal cells.…”

Section: Discussionmentioning

confidence: 99%

Cancer-associated hypersialylated MUC1 drives the differentiation of monocytes into macrophages with a pathogenic phenotype

Beatson

Graham

Grundland-Freile

et al. 2020

Preprint

View full text Add to dashboard Cite

The tumour microenvironment plays a crucial role in the growth and progression of cancer and the presence of tumour-associated macrophages (TAMs) is associated with poor prognosis. Recent studies show that TAMs show transcriptomic, phenotypic, functional and geographical diversity. Here we show that a sialylated tumour-associated glycoform of the mucin MUC1, MUC1-ST, through the engagement of Siglec-9 can specifically and independently induce the differentiation of monocytes into TAMs with a unique phenotype.These TAMs can recruit and maintain neutrophils, inhibit the function of T cells, degrade

show abstract

Distinct prognostic values of S100 mRNA expression in breast cancer

Cited by 72 publications

References 67 publications

S100A10 has a Critical Regulatory Function in Mammary Tumor Growth and Metastasis: Insights using MMTV-PyMT Oncomice and Clinical Patient Sample Analysis.

S100A10 has a Critical Regulatory Function in Mammary Tumor Growth and Metastasis: Insights using MMTV-PyMT Oncomice and Clinical Patient Sample Analysis.

Changes in Serum and Salivary Proteins in Canine Mammary Tumors

Cancer-associated hypersialylated MUC1 drives the differentiation of monocytes into macrophages with a pathogenic phenotype

Contact Info

Product

Resources

About