Evaluation of the expression of stem cell markers in human breast cancer reveals a correlation with clinical progression and metastatic disease in ductal carcinoma

Abstract

Abstract. The tumor stem cell theory could explain how patients with metastatic disease show clinical relapse several months after starting treatment due to the survival of a small group of cells with unique characteristics. We examined the distribution and expression of a panel of stem cell markers in human breast cancer primary tumors. Human breast tissues were processed for immunohistochemistry, and RNA was extracted for analysis by quantitative-PCR. Immunohistochemical assay revealed that CD44 was strongly expressed in background endothelia and epithelia. CD133 expression was lost in tumor-associated endothelial cells. Conversely, CD49b was strongly stained in the tumors, associated vessels and ducts but was weakly stained in the background epithelia. q-PCR analysis revealed that CD44 and PSCA were reduced in patients with poor outcome (metastatic disease and death from breast cancer), with a marked reduction in ductal carcinoma, particularly with metastasis to bone although these did not reach significant difference. CD133 was significantly reduced in patients with metastatic disease and was also significantly reduced in patients with ductal carcinoma/bone metastasis. Conversely, CD49F was increased in patients with a poor outcome and those with ductal cancer and bone metastases. This is the first study to determine the distribution and expression pattern of these stem cell markers in human breast cancer. There was a significant association between loss of expression and metastatic disease in patients with breast cancer. Such differential expression may play a part in breast cancer disease progression, and suggests that the current stem cell theory may not hold true for all cancer types.

The clinicopathological and prognostic significance of CD24, CD44, CD133, ALDH1 expressions in invasive ductal carcinoma of the breast

“…In this study there was high CD133 expression in only 1 out of 16 triple negative cancers and which is in contrast to the study of Zhao et al CD133 expression was decreased in tumors with lymphovascular invasion, larger tumor size and higher stage. Martin et al [36] recently indicated that the CD133 expression is reduced in patients with metastatic disease, which supports our findings. On the other hand high CD133 expression was positively correlated with CD44 + and CD44 + /CD24 + expressions.…”

Chemotherapy of WAP‐T mouse mammary carcinomas aggravates tumor phenotype and enhances tumor cell dissemination

“…Additionally, the expression of stem cell factors increased after CAF treatment in vitro, which relates to poor prognosis and increased risk of metastases. 24,25 Therefore, application of chemotherapy leads to a more mesenchymal tumor phenotype in this model. A mesenchymal phenotype of epithelial tumors corresponds to higher aggressiveness and poor prognosis.…”

Tension in Cancer

“…Consistent with their essential role in cell adhesion to the extracellular matrix, dysregulation of integrin expression and their associated signalling pathways have been associated with pathological states such as carcinogenesis and the metastatic spread of tumor cells [44,45,46,47,48]. Although the above mentioned examples portray the complexity and dynamics of integrin-signalling, particularly in the context of carcinogenesis and tumor cell progression, interfering with integrin-ECM interactions appears to be an auspicious strategy for the development of therapeutic agents (Table 2).…”

“…The α6-subunit is enriched in TICs in breast, prostate and colorectal cancers [44,46,49] as well as squamous cell carcinoma [48] and is important for the maintenance of glioblastoma stem cells [45]. Likewise, the expression of the β4-subunit has been described to serve as a marker for the propagation of lung cancer cells [50].…”