CD44 induces FOXP3 expression and is related with favorable outcome in breast carcinoma.

Abstract

We studied the relationship between CD44 and Forkhead box P3 (FOXP3) gene expression in cell lines and breast carcinomas and their association with clinicopathological variables and patient outcome. We assessed messenger RNA (mRNA) expression of CD44 and FOXP3 by quantitative real-time PCR and determined the number of FOXP3+ Tregs by immunohistochemistry in 264 breast cancer specimens. CD44 was stimulated with hyaluronan treatment, and the accompanying changes in FOXP3 mRNA expression in breast cancer cell lines representing breast cancer subtype were assessed. We found that lower CD44 expression correlated with the presence of necrosis, lymph-vascular invasion, grade 3 tumors, and aggressive phenotype (HER2 and basal-like). FOXP3 mRNA correlated positively with CD44 mRNA expression and Treg content. Moreover, stimulation of CD44 expression by hyaluronan in cell lines increased FOXP3 expression, which supports that their regulation is associated. Survival analysis revealed that low CD44 expression is associated with higher frequency of recurrence. Our findings indicate that CD44 has a regulatory role in FOXP3 expression and is associated with good prognostic factors in breast cancer.

• Authors: Elena Sanmartín, Fernando Ortiz-Martínez, Eloy Pomares-Navarro, Araceli García-Martínez, Montserrat Rodrigo-Baños, Marta García-Escolano, Leire Andrés, Enrique Lerma, Francisco I Aranda, Pascual Martínez-Peinado, José M Sempere-Ortells, Gloria Peiró
• Journal: Virchows Archiv : an international journal of pathology (Virchows Arch) Vol. 470 Issue 1 Pg. 81-90 (Jan 2017) ISSN: 1432-2307 [Electronic] Germany
• PMID: 27885422 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• CD44 protein, human
• FOXP3 protein, human
• Forkhead Transcription Factors
• Hyaluronan Receptors

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (analysis)
• Breast Neoplasms (metabolism, pathology)
• Disease-Free Survival
• Female
• Forkhead Transcription Factors (metabolism)
• Humans
• Hyaluronan Receptors (metabolism)
• Immunohistochemistry (methods)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (diagnosis, metabolism, pathology)
• Prognosis
• T-Lymphocytes, Regulatory (metabolism)
• Young Adult