Lactadherin: From a Well-Known Breast Tumor Marker to a Possible Player in Extracellular Vesicle-Mediated Cancer Progression.

Lactadherin is a secreted glycoprotein associated with the milk fat globule membrane, which is highly present in the blood and in the mammary tissue of lactating women. Several biological functions have been associated with this protein, mainly attributable to its immunomodulatory role promoting phagocyte-mediated clearance of apoptotic cells. It has been shown that lactadherin also plays important roles in cell adhesion, the promotion of angiogenesis, and tissue regeneration. On the other hand, this protein has been used as a marker of breast cancer and tumor progression. Recently, high levels of lactadherin has been associated with poor prognosis and decreased survival, not only in breast cancer, but also in melanoma, ovarian, colorectal, and other types of cancer. Although the mechanisms responsible for the tumor-promoting effects attributed to lactadherin have not been fully elucidated, a growing body of literature indicates that lactadherin could be a promising therapeutic target and/or biomarker for breast and other tumors. Moreover, recent studies have shown its presence in extracellular vesicles derived from cancer cell lines and cancer patients, which was associated with cancer aggressiveness and worse prognosis. Thus, this review will focus on the link between lactadherin and cancer development and progression, its possible use as a cancer biomarker and/or therapeutic target, concluding with a possible role of this protein in cellular communication mediated by extracellular vesicles.

Stocking density induces differential expression of immune-related genes in skeletal muscle and head kidney of fine flounder (Paralichthys adspersus).

Immunity can be modulated by different internal and external factors, being stress one of the most important. However, the stress effects on the immunocompetence of the skeletal muscle has not been studied in detail in earlier vertebrates. Here, we examine the effect of chronic (4 and 7 weeks) crowding stress on the immunocompetence of skeletal muscle and head kidney in the fine flounder (Paralichthys adspersus). Corticosteroid receptor transcript levels and their target genes; pro-inflammatory cytokines, and Toll-, NOD-, and RIG-like receptors were quantified by qPCR. The results indicate that chronic stress down-regulates the expression of these genes in muscle, compromising skeletal muscle immunocompetence, while the expression of these genes is upregulated in head kidney after seven weeks of crowding stress. The data suggests that chronic stress modulates the expression of these immune-related genes in a tissue-specific manner.

Fish skeletal muscle tissue is an important focus of immune reactions during pathogen infection.

Skeletal muscle in mammals can express and secrete immune-related molecules during pathogen infection. Despite in fish is known that classical immune tissues participate in innate immunity, the role of skeletal muscle in this function is poorly understood. To determine the immunocompetence of fish skeletal muscle, juvenile fine flounder (Paralichthys adpersus) were challenged with Vibrio ordalii. Different Toll-like receptors, pro-inflammatory cytokines (TNFα, Il-1ß, and IL-8), and immune-effector molecules (NKEF and the antimicrobial peptides hepcidin and LEAP-2) were analyzed. Infection initially triggered IL-1ß upregulation and P38-MAPK/AP-1 pathway activation. Next, the NFĸB pathway was activated, together with an upregulation of intracellular Toll-like receptor expressions (tlr3, tlr8a tlr9, and tlr21), TNFα production, and leap-2 expression. Finally, transcriptions of il-1ß, il-8, tnfα, nkef-a, and hepcidin were also upregulated. These results suggest that fish skeletal muscle is an immunologically active organ that could play an important role against pathogens.