Shallow marine sequences of the northern South China Sea (SCS) are uplifted and exposed by plate convergence in the Taiwan mountain belt. These deposits provide detailed geological information about the rifting event, stratigraphy, sedimentology, paleoclimate and paleoceanography of the shallow SCS to compare with what are recorded in the ODP 1148 deep-sea core. Seismic surveys and marine micropalentological studies show that Eocene sequences in the offshore Taiwan Strait and onland Taiwan mountain belt are all deposited in rifting basins and are covered unconformably by the Late Oligocene-Neogene post-rifting strata. Between syn-rifting and post-rifting sequences, there is a regional break-up unconformity throughout the island. Early Oligocene and Late Eocene strata are missing along the break-up unconformity equivalent to the T 7 unconformity in the Pearl River Mouth Basin off south China. This may suggest that the SCS oceanic crust could have initiated between 33 and 39 Ma. Neither obvious stratigraphic gap nor slumping features are found in the Oligocene-Miocene transition interval of Taiwan. This observation highly contrasts with what has been documented from the ODP 1148 deep-sea core. This suggests that the stratigraphic gap and slumping features could only be recorded in the SCS deep sea region, but not in the shallow shelf near Taiwan. Compared to the Middle Miocene paleoceanographic re-organization events in the SCS deep sea, the geological history of the Taiwan shallow sequence shows changes of in sedimentation and faunal composition. Due to the Antarctic glacial expansion at ~14 Ma, Middle to late Miocene strata of the Western Foothills show progressive regression sedimentations associated with a decrease of benthic foraminiferal abundance and a sharp faunal turnover event. Many Early-Middle Miocene endemic benthic foraminifers were extinct in 14-13 Ma and new benthic foraminifers of the Kuroshio Current fauna appeared from 10.2 Ma, comparable with new occurrence of Modern benthic foraminifers at 9 Ma in the Java Sea area. This reveals that the Western Boundary Kuroshio Current in the North Pacific could initiate from 10-9 Ma due to closures of the Indo-Pacific seaways by convergent tectonics between the Australian Continent and the Indonesian Arc in 12-8 Ma. Subduction of the SCS oceanic lithosphere since the Middle Miocene resulted in formation of the Hengchun Ridge accretionary prism and the North Luzon Arc. Occurrence of these two bathymetric highs (2400 m) since the Middle Miocene and closures of the inter-arc passages in the North Luzon arc in the last 3.5 Ma would control the water exchanges between the West Pacific and the deep SCS. Accordingly, the tectonic evolution in the Central Range-Hengchun Peninsula accretionary prism and the arc-forearc Coastal Range not only control directly the route for water exchanges between the West Pacific and the SCS, but also indirectly shows a great influence on the geochemistry of deep SCS waters. The latter is best shown by much negative carbon isotope v...

Background Expression of Oct4 maintains cancer stem cell (CSC)-like properties in lung cancer cells and is correlated with poor prognosis of lung adenocarcinoma. M2-type tumor-associated macrophages (TAMs) promote cancer cell migration and metastasis. Tumor microenvironments promote monocyte differentiation into M2 TAMs via a complex cytokine-based connection. We explored the role of Oct4 in cytokine secretion in lung cancer and its impact on M2 TAM polarization. Methods Monocytes co-cultured with the conditioned medium from Oct4-overexpressing lung cancer cells were used to investigate M2 TAM differentiation. The inflammatory factors in the conditioned medium of Oct4-overexpressing A549 cells were examined using human inflammation antibody arrays. The correlations of Oct4, macrophage colony-stimulating factor (M-CSF), and M2 TAMs were validated in lung cancer cells, syngeneic mouse lung tumor models, and clinical samples of non-small cell lung cancer (NSCLC). Results Oct4-overexpressing A549 cells expressed elevated levels of M-CSF, which contributed to increased M2 macrophages and enhanced tumor migration. Overexpression of Oct4 enhanced tumor growth and reduced the survival of lung tumor-bearing mice, which was correlated with increased number of M2 macrophages in lung cancer. Notably, NSCLC patients with high expression levels of Oct4, M-CSF, and M2 TAMs had the poorest recurrence-free survival. A positive correlation between Oct4, M-CSF, and M2 TAMs was observed in the tumor tissue of NSCLC patient. Treatment with all-trans retinoic acid exerted anti-tumor effects and reduced M2 TAMs in tumor-bearing mice. Conclusions Our results indicate that Oct4 expressed by lung cancer cells promotes M2 macrophage polarization through upregulation of M-CSF secretion, leading to cancer growth and metastasis. Our findings also implicate that the Oct4/M-CSF axis in M2 macrophage polarization may be potential therapeutic targets for lung cancer.

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