RESUMO

BACKGROUND AND AIMS: Calreticulin is a chaperone and master regulator of intracellular calcium homeostasis. Several additional functions have been discovered. Human and parasite calreticulin have been shown to suppress mammary tumor growth in vivo. Here, we explored the capacity of recombinant Taenia solium calreticulin (rTsCRT) to modulate cancer cell growth in vitro. METHODS: We used different concentrations of rTsCRT to treat cancer cell lines and analyzed viability and colony formation capacity. We also tested the combination of the IC20 or IC50 doses of rTsCRT and of the chemotherapeutic drug 5-fluorouracil on MCF7 and SKOV3 cell lines. As a control, the non-tumorigenic cell line MCF10-A was employed. The effect of the drug combinations was also assessed in cancer stem-like cells. Additionally, scavenger receptor ligands were employed to identify the role of this receptor in the rTsCRT anti-tumoral effect. RESULTS: rTsCRT has a dose-dependent in vitro anti-tumoral effect, being SKOV3 the most sensitive cell line followed by MCF7. When rTsCRT/5-fluorouracil were used, MCF7 and SKOV3 showed a 60% reduction in cell viability; colony formation capacity was also diminished. Treatment of cancer stem-like cells from MCF7 showed a higher reduction in cell viability, while those from SKOV3 were more sensitive to colony disaggregation. Finally, pharmacological inhibition of the scavenger receptor, abrogated the reduction in viability induced by rTsCRT in both the parental and stem-like cells. CONCLUSION: Our data suggest that rTsCRT alone or in combination with 5-fluorouracil inhibits the growth of breast and ovarian cancer cell lines through its interaction with scavenger receptors.

Assuntos

Neoplasias da Mama/tratamento farmacológico , Calreticulina/uso terapêutico , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Calreticulina/genética , Calreticulina/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Sinergismo Farmacológico , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Células HeLa , Humanos , Células MCF-7 , Células-Tronco Neoplásicas/metabolismo , Neoplasias Ovarianas/patologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Taenia solium/genética

RESUMO

Calreticulin (CRT) is a pleiotropic and highly conserved molecule that is mainly localized in the endoplasmic reticulum. Recently, CRT has gained special interest for its functions outside the endoplasmic reticulum where it has immunomodulatory properties. CRT translocation to the cell membrane serves as an "eat me" signal and promotes efferocytosis of apoptotic cells and cancer cell removal with completely opposite outcomes. Efferocytosis results in a silenced immune response and homeostasis, while removal of dying cancer cells brought about by anthracycline treatment, ionizing-irradiation or photodynamic therapy results in immunogenic cell death with activation of the innate and adaptive immune responses. In addition, CRT impacts phagocyte activation and cytokine production. The effects of CRT on cytokine production depend on its conformation, species specificity, degree of oligomerization and/or glycosylation, as well as its cellular localization and the molecular partners involved. The controversial roles of CRT in cancer progression and the possible role of the CALR gene mutations in myeloproliferative neoplasms are also addressed. The release of CRT and its influence on the different cells involved during efferocytosis and immunogenic cell death points to additional roles of CRT besides merely acting as an "eat me" signal during apoptosis. Understanding the contribution of CRT in physiological and pathological processes could give us some insight into the potential of CRT as a therapeutic target.

Assuntos

Calreticulina/imunologia , Imunidade/imunologia , Neoplasias/imunologia , Fagocitose/imunologia , Animais , Membrana Celular/imunologia , Retículo Endoplasmático/imunologia , Humanos

RESUMO

BACKGROUND: Newborn hyperbilirubinemia is considered a worldwide health problem that demands medical evaluation. Noninvasive transcutaneous bilirubin (TcB) has been used as a screening method with different devices but there has not been any evaluation of reproducibility of the same brand devices. The BiliCare™ system is evaluated to demonstrate consistency between measurements with four different devices. METHODS: 336 TcB measurements were obtained with four BiliCare™ devices in 21 Mexican icteric newborns with a mean postnatal age of 44.1 hours of life and 38 weeks of gestation (33-41). Two measurements were taken in the same ear alternatively at the scaphoid fossa with each device. TcB values were compared between devices. Validity was compared with total serum bilirubin (TB). RESULTS: intraclass correlation coefficient demonstrates a minimum limit in the study of 0.945 and maximum of 0.988 with the same device. Correlations with serum and between devices gave results above 0.932. CONCLUSIONS: BiliCare™ transcutaneous bilirubin measurement instrument has very good intra- and interdevice reproducibility; also correlation of TcS with serum bilirubin gave statistically the same results.