Osteopontin, also called secreted phosphoprotein 1 (SPP1), is a multifunctional secreted phosphorylated glycoprotein. SPP1 is also expressed in tumor cells, and many studies demonstrated that a high level of circulating SPP1 is correlated with a poor prognosis in various cancers. SPP1 is expressed not only by tumor cells but also by stromal cells, such as macrophages. However, there have been no studies distinguishing the SPP1 expression of cancer cells and tumor-associated macrophages (TAMs). Thus, in this study, we tried to accurately evaluate the SPP1 expression status on cancer cells and TAMs separately in patients with non-small cell lung cancer by using double immunohistochemistry. We demonstrated that high SPP1 expression on TAMs predicted a poor prognosis in lung adenocarcinoma patients. Additionally, we investigated the expression mechanisms related to SPP1 using human-monocyte-derived macrophages and revealed that the SPP1 expression level increased in macrophage differentiation mediated by granulocyte-macrophage colony-stimulating factor. Furthermore, SPP1 contributed to anti-cancer drug resistance in lung cancer cell lines. In conclusion, SPP1 production on TAMs predicted a poor prognosis in lung adenocarcinoma patients, and TAM-derived SPP1′s involvement in the chemo-resistance of cancer cells was suggested.

We recently discovered a novel neuropeptide of 80 amino acid residues: neurosecretory protein GL (NPGL), in the hypothalamus of birds and rodents. NPGL is localized in the lateral posterior part of the arcuate nucleus (ArcLP), and it enhances feeding behavior and fat accumulation in mice. Various neurotransmitters, such as catecholamine, glutamate, and γ-aminobutyric acid (GABA), produced in the hypothalamus are also involved in energy metabolism. The colocalization of neurotransmitters and NPGL in neurons of the ArcLP leads to the elucidation of the regulatory mechanism of NPGL neurons. In this study, we performed double immunofluorescence staining to elucidate the relationship between NPGL and neurotransmitters in mice. The present study revealed that NPGL neurons did not co-express tyrosine hydroxylase as a marker of catecholaminergic neurons and vesicular glutamate transporter-2 as a marker of glutamatergic neurons. In contrast, NPGL neurons co-produced glutamate decarboxylase 67, a marker for GABAergic neurons. In addition, approximately 50% of NPGL neurons were identical to GABAergic neurons. These results suggest that some functions of NPGL neurons may be related to those of GABA. This study provides insights into the neural network of NPGL neurons that regulate energy homeostasis, including feeding behavior and fat accumulation.

Intermediate progenitors of both excitatory and inhibitory neurons, which can replenish neurons in the adult brain, were recently identified. However, the generation of intermediate progenitors of GABAergic inhibitory neurons (IPGNs) has not been studied in detail. Here, we characterized the spatiotemporal distribution of IPGNs in mouse cerebral cortex. IPGNs generated neurons during both embryonic and postnatal stages, but the embryonic IPGNs were more proliferative. Our lineage tracing analyses showed that the embryonically proliferating IPGNs tended to localize to the superficial layers rather than the deep cortical layers at 3 weeks after birth. We also found that embryonic IPGNs derived from the medial and caudal ganglionic eminence (CGE) but more than half of the embryonic IPGNs were derived from the CGE and broadly distributed in the cerebral cortex. Taken together, our data indicate that the broadly located IPGNs during embryonic and postnatal stages exhibit a different proliferative property and layer distribution.

The retroesophageal right subclavian artery (RRSA) is a congenital anomalous branching of the arch of the aorta. Because its incidence is very low, it has not been fully understood how the RRSA develops during embryogenesis, and thus accumulation of observed findings in newly found cases is important to elucidate the etiology of the RRSA. We encountered a case of the RRSA during the course of gross anatomy dissection for medical students. The main findings in the present observations are that (a) the RRSA arose from the right side wall of the arch of the aorta as its last branch; (b) the detected RRSA was directed to the right and upward between the esophagus and vertebral column; (c) the right vertebral artery branched from the RRSA and entered the sixth cervical foramen transversarium; (d) the suprema intercostal artery branched from the costocervical trunk on both sides and its distal branches were distributed to the first and second intercostal spaces; and (e) both sides of bronchial arteries originated from the thoracic aorta. The present study gives further information about the morphological details of the RRSA leading to better understanding of its developmental process. The retroesophageal right subclavian artery (RRSA) is a congenital anomalous branching of the arch of the aorta. Because its incidence is very low, it has not been fully understood how the RRSA develops during embryogenesis, and thus accumulation of observed findings in newly found cases is important to elucidate the etiology of the RRSA. We encountered a case of the RRSA during the course of gross anatomy dissection for medical students. The main findings in the present observations are that (a) the RRSA arose from the right side wall of the arch of the aorta as its last branch; (b) the detected RRSA was directed to the right and upward between the esophagus and vertebral column; (c) the right vertebral artery branched from the RRSA and entered the sixth cervical foramen transversarium; (d) the suprema intercostal artery branched from the costocervical trunk on both sides and its distal branches were distributed to the first and second intercostal spaces; and (e) both sides of bronchial arteries originated from the thoracic aorta. The present study gives further information about the morphological details of the RRSA leading to better understanding of its developmental process.