Background and Aim: The study of CD44/CD24 and ALDH1 expression is the most accurate method to identify cancer stem cells (CSC) from breast cancer populations. However, the overlap between CD44⁺CD24^−/low and ALDH1^high CSC phenotypes in breast cancer seems to be very small, as well as their distribution among intrinsic breast cancer subtypes. Due to this discrepancy, it is imperative to improve the understanding of breast CSC marker distribution. Methods: 466 invasive breast carcinomas and eight breast cancer cell lines were analysed for the expression of CD44, CD24 and ALDH1, to evaluate their distribution among the distinct molecular subtypes. Results: Basal-like tumours (76.5%) contained the higher percentage of cells with the CSC phenotype CD44⁺CD24^−/low (p<0.0001). From ALDH1-positive cases, 39.4% were also basal-like tumours (p<0.0001). The analysis of breast cancer cell lines indicated that luminal cell lines are mainly enriched in a CD44^−/lowCD24⁺ cell population, basal/mesenchymal breast cancer cell lines are enriched in the CD44⁺CD24^−/low phenotype, whereas the remaining basal/epithelial cell lines are mainly positive for both markers. ALDH1 activity was mainly found in HER-OE and basal/epithelial breast cancer cell. Conclusions: CD44⁺CD24^−/low and ALDH1⁺ phenotypes seem to identify CSC with distinct levels of differentiation. It seems that the paramount method and biomarkers that identify breast CSC within the distinct molecular subtypes need to be better explored, because it is pivotal to translate the CSC concept to clinical practice. In the future, the recognition of reliable markers to distinguish the CSC pool in each molecular subtype will be decisive for the development of specific target therapies.

Monocarboxylate transporters (MCTs) are important cellular pH regulators in cancer cells; however, the value of MCT expression in cancer is still poorly understood. In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44. MCT expression frequency was high and heterogeneous among the different tumours. Comparing with normal tissues, there was an increase in MCT1 and MCT4 expressions in breast carcinoma and a decrease in MCT4 plasma membrane expression in lung cancer. There were associations between CD147 and MCT1 expressions in ovarian cancer as well as between CD147 and MCT4 in both breast and lung cancers. CD44 was only associated with MCT1 plasma membrane expression in lung cancer. An important number of MCT1 positive cases are negative for both chaperones, suggesting that MCT plasma membrane expression in tumours may depend on a yet nonidentified regulatory protein.

Ovarian cancer (OC) has a specific type of metastasis, via transcoelomic, and most of the patients are diagnosed at advanced stages with multiple tumors spread within the peritoneal cavity. The role of Malignant Ascites (MA) is to serve as a transporter of tumor cells from the primary location to the peritoneal wall or to the surface of the peritoneal organs. MA comprise cellular components with tumor and non-tumor cells and acellular components, creating a unique microenvironment capable of modifying the tumor behavior. These microenvironment factors influence tumor cell proliferation, progression, chemoresistance, and immune evasion, suggesting that MA play an active role in OC progression. Tumor cells induce a complex immune suppression that neutralizes antitumor immunity, leading to disease progression and treatment failure, provoking a tumor-promoting environment. In this review, we will focus on the High-Grade Serous Carcinoma (HGSC) microenvironment with special attention to the tumor microenvironment immunology.

Although the luminal progenitor cell of the normal mammary gland hierarchy has been proposed as the cell‐of‐origin for basal‐like breast cancers, finding the cancer stem cell (CSC) phenotype for this malignancy has proven a difficult task, mostly due to the lack of specific markers. Recently, basal‐like sporadic and familial cases of breast cancer have been linked to BRCA1 gene inactivation, which enables the upregulation of the target‐repressed CDH3/P‐cadherin gene, an important biomarker of basal‐like breast carcinomas. Previously, we demonstrated that P‐cadherin overexpression can mediate aggressive behavior in these tumors. Thus, our aim was to test whether P‐cadherin mediates stem cell properties in basal‐like breast carcinomas. Using a series of breast cancer cell lines and primary tumors, we showed that P‐cadherin was directly associated with the expression of the breast stem markers CD44, CD49f, and aldehyde dehydrogenase 1 in the basal subtype. Moreover, cell population enriched for P‐cadherin expression comprised increased in vitro mammosphere‐forming efficiency and capacity to grow colonies in three‐dimensional cultures as well as greater tumorigenicity. Importantly, an association was found with stem‐/progenitor‐like phenotypes of the breast, including the luminal progenitor population, CD49f⁺CD24⁺. Additionally, P‐cadherin expression conferred resistance to x‐ray‐induced cell death, sustaining a role for this molecule in another stem cell property. In summary, we demonstrated, for the first time, that P‐cadherin mediates stem cell properties, which could be explored in order to better define the CSC phenotype of basal‐like breast tumors and the cell‐of‐origin of this malignancy. STEM CELLS 2012;30:854–864