No abstract

In order to study how adipose conversion affects the extracellular environment, levels of extracellular matrix (ECM) proteins during differentiation were analyzed by 125I-labeled antibody binding to each specific primary antibody. When confluent bovine intramuscular preadipocytes (BIP) were stimulated with adipogenic medium, there was a significant accretion on the cell surface of type I-VI collagens, laminin and fibronectin, compared with undifferentiated cells. The deposition amount of ECM proteins had reached near maximal levels at an early stage of differentiation and lasted throughout the culture. However, the increasing manners were not all the same in these eight proteins. Type V and type VI collagen tended to show a transient decline after the rapid rise at the beginning of stimulation, and fibronectin instead, subsequently decreased. Further analysis by immunocytochemical staining showed that remodeling occurred in type V and VI collagen matrices during this period; extensive fibrillar networks seen at 10 d after stimulation were quite unlike that formed earlier. These specific increases and development of matrix during adipocyte differentiation imply some significance for organizing fat lobules in each ECM proteins, especially type V and VI collagens.

Bone morphogenetic protein (BMP) signaling exerts antitumor activities in glioblastoma; however, its precise mechanisms remain to be elucidated. Here, we demonstrated that the BMP type I receptor ALK-2 (encoded by the ACVR1 gene) has crucial roles in apoptosis induction of patient-derived glioma-initiating cells (GICs), TGS-01 and TGS-04. We also characterized a BMP target gene, Distal-less homeobox 2 (DLX2), and found that DLX2 promoted apoptosis and neural differentiation of GICs. The tumor-suppressive effects of ALK-2 and DLX2 were further confirmed in a mouse orthotopic transplantation model. Interestingly, valproic acid (VPA), an anti-epileptic compound, induced BMP2, BMP4, ACVR1 and DLX2 mRNA expression with a concomitant increase in phosphorylation of Smad1/5. Consistently, we showed that treatment with VPA induced apoptosis of GICs, whereas silencing of ALK-2 or DLX2 expression partially suppressed it. Our study thus reveals BMP-mediated inhibitory mechanisms for glioblastoma, which explains, at least in part, the therapeutic effects of VPA.

No abstract

BMP signaling has been found to have tumor-promoting as well as tumor-suppressing effects in different types of tumors. In this study, we investigated the effects of BMP signaling and of BMP inhibitors on ovarian cancer (OC) cells in vitro and in vivo. High expression of BMP receptor 2 (BMPR2) correlated with poor overall survival of OC patients in the TCGA dataset. Both BMP2 and BMPR2 enhanced OC cell proliferation, whereas BMP receptor kinase inhibitors inhibited OC cell growth in cell culture as well as in a mouse model. BMP2 also augmented sphere formation, migration, and invasion of OC cells, and induced EMT. High BMP2 expression was observed after chemotherapy of OC patients in the GSE109934 dataset. In accordance, carboplatin, used for the treatment of OC patients, increased BMP2 secretion from OC cells, and induced EMT partially via activation of BMP signaling. Our data suggest that BMP signaling has tumor-promoting effects in OC, and that BMP inhibitors might be useful therapeutic agents for OC patients. Considering that carboplatin treatment augmented BMP2 secretion, the possibility to use a combination of BMP inhibitors and carboplatin in the treatment of OC patients, would be worth exploring.

ABSTRACT. Silky fowl, a breed of chicken, is hyperpigmented in its various internal tissues. The pigment was extracted from various tissues of two strains of Silky fowl to determine its molecular structure and internal distribution. Analysis by infrared spectroscopy showed two spectrum patterns of the pigment in Silky fowl; one is from ovary and testis, the other is from periosteum and feather. The difference between the two spectra is possibly due to the sulfur contents of melanin. Especially, the spectra of the pigments from feather and periosteum shared the characteristics of synthesized melanin spectrum in common, which indicates that the melanocytes dispersed in these tissues were functionally the same. According to our quantitative analysis, the tissues examined were classified significantly in the order of the pigment content (p<0.05): periosteum > gonads (ovary or testis) = trachea ≥ heart, liver, gizzard, cecum, muscles (Pectoralis and Supracoracoideus) and skin. In addition, the specific regions of embryonic neural crest derived cells, such as cardiac artery and various parts of cephalic tissues, were found to be locally hyperpigmented. These data suggest that hyperpigmentation (fibromelanosis) in Silky fowl chicken occurs in a tissue-and organ-specific manner, which is strongly related to neural crest cell development. It is hypothesized that neural crest cells of the bird, containing melanocyte progenitors, acquire unusual ability to differentiate into melanocytes excessively, and to extend the distribution of their descendant along the destinations of neural crest derivatives.-KEY WORDS: hyperpigmentation, melanocyte, neural crest, pigment distribution, Silky fowl.

No abstract

Development of innovative therapeutic modalities would address an unmet clinical need in the treatment of triple negative breast cancer (TNBC). Activation of retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) such as melanoma differentiation-associated gene 5 (MDA5) and RIG-I in cancer cells is suggested to suppress tumor progression by inducing cell death. Transfection of polyI:C, a conventionally used synthetic double-stranded RNA (dsRNA) analogue that activates RLRs, has been evaluated in clinical trials. However, detailed mechanisms of tumor suppression by RLRs, especially interactions with other signaling pathways, remain elusive. Here, we showed that transfection of polyI:C suppressed transforming growth factor-b (TGF-b) signaling in a MDA5-and RIG-I-dependent manner. We found that suppression of TGF-b signaling by polyI:C promoted cancer cell death, which was attenuated by forced expression of constitutively active Smad3. More detailed analysis suggested that cell death by polyI:C transfection exhibited characteristics of pyroptosis, which is distinct from apoptosis. Therapeutic efficacy of polyI:C transfection was also demonstrated using a mouse model. These results indicated that intratumor administration of polyI:C and related dsRNA analogues may be promising treatments for TNBC through inhibition of the anti-pyroptotic function of TGF-b.