Endothelin (ET)-1 contributes to melanoma progression via cell proliferation, invasion, and migration. We previously reported that annexin A2 (AnxA2) binds to ET receptors. In this study, we aimed to further investigate role of AnxA2 in melanoma cell proliferation after ET-1 stimulation.
View Article and Find Full Text PDFWhereas extracellular vesicles (EVs) have been engineered for cargo loading, innovative strategies for it can still be developed. Here, we describe domain 4 (D4), a cholesterol-binding domain derived from perfringolysin O, as a viable candidate for EV cargo loading. D4 and its mutants localized to the plasma membrane and the membranes of different vesicular structures in the cytoplasm, and facilitate the transport of proteins of interest (POIs) into EVs.
View Article and Find Full Text PDFIn lung cancer, immune checkpoint inhibitors (ICIs) are often inadequate for tumor growth inhibition. Angiogenic inhibitors (AIs) are required to normalize tumor vasculature for improved immune cell infiltration. However, in clinical practice, ICIs and cytotoxic antineoplastic agents are simultaneously administered with an AI when tumor vessels are abnormal.
View Article and Find Full Text PDFEpidemiological relationships between cancer and cardiovascular diseases have been reported, but a molecular basis remains unclear. Some proteoglycans that strongly bind low-density-lipoprotein (LDL) are abundant both in atherosclerotic regions and in high metastatic-tumor tissue. LDL retention is crucial for the initiation of atherosclerosis, although its contribution to malignancy of cancer is not known.
View Article and Find Full Text PDFThis study investigated variations in the relative biological effectiveness (RBE) values among various sarcoma and normal-tissue-derived cell lines (normal cell line) in proton beam and carbon-ion irradiations. We used a consistent protocol that specified the timing of irradiation after plating cells and detailed the colony formation assay. We examined the cell type dependence of RBE for proton beam and carbon-ion irradiations using four human sarcoma cell lines (MG63 osteosarcoma, HT1080 fibrosarcoma, SW872 liposarcoma, and SW1353 chondrosarcoma) and three normal cell lines (HDF human dermal fibroblast, hTERT-HME1 mammary gland, and NuLi-1 bronchus epithelium).
View Article and Find Full Text PDFHypoxia is associated with tumor radioresistance; therefore, a predictive marker for tumor hypoxia and a rational target to overcome it have been sought to realize personalized radiotherapy. Here, we show that serine protease inhibitor Kazal type I (SPINK1) meets these 2 criteria. SPINK1 expression was induced upon hypoxia (O2 < 0.
View Article and Find Full Text PDFHypoxia, a characteristic feature of solid tumors, is associated with the malignant phenotype and therapy resistance of cancers. Hypoxia-inducible factor 1 (HIF-1), which is responsible for the metazoan adaptive response to hypoxia, has been recognized as a rational target for cancer therapy due to its critical functions in hypoxic regions. In order to efficiently inhibit its activity, extensive efforts have been made to elucidate the molecular mechanism underlying the activation of HIF-1.
View Article and Find Full Text PDFMetastasis is not the result of a random event, as cancer cells can sustain and proliferate actively only in a suitable tissue microenvironment and then form metastases. Since Dr. Stephen Paget in the United Kingdom proposed the seed and soil hypothesis of cancer metastasis based on the analogy that plant seeds germinate and grow only in appropriate soil, considerable attention has focused on both extracellular environmental factors that affect the growth of cancer cells and the tissue structure that influences the microenvironment.
View Article and Find Full Text PDFBackground: Biglycan is a proteoglycan found in the extracellular matrix. We have previously shown that biglycan is secreted from tumor endothelial cells and induces tumor angiogenesis and metastasis. However, the function of stroma biglycan in breast cancer is still unclear.
View Article and Find Full Text PDFBackground: Radiotherapy is the standard treatment for glioblastoma (GBM). However, radioresistance of GBM cells leads to recurrence and poor patient prognosis. Recent studies suggest that secretion factors have important roles in radioresistance of tumor cells.
View Article and Find Full Text PDFEnhanced invasiveness, a critical determinant of metastasis and poor prognosis, has been observed in cancer cells that survive cancer therapy, including radiotherapy. Here, we show that invasiveness in radiation-surviving cancer cells is associated with alterations in lysosomal exocytosis caused by the enhanced activation of Arl8b, a small GTPase that regulates lysosomal trafficking. The binding of Arl8b with its effector, SKIP, is increased after radiation through regulation of BORC-subunits.
View Article and Find Full Text PDFPurpose: The purpose of this study is to evaluate the sublethal damage (SLD) repair effect in prolonged proton irradiation using the biophysical model with various cell-specific parameters of (α/β) and T (repair half time). At present, most of the model-based studies on protons have focused on acute radiation, neglecting the reduction in biological effectiveness due to SLD repair during the delivery of radiation. Nevertheless, the dose-rate dependency of biological effectiveness may become more important as advanced treatment techniques, such as hypofractionation and respiratory gating, come into clinical practice, as these techniques sometimes require long treatment times.
View Article and Find Full Text PDFBackground: Tumor endothelial cells (TECs) perform tumor angiogenesis, which is essential for tumor growth and metastasis. Tumor cells produce large amounts of lactic acid from glycolysis; however, the mechanism underlying the survival of TECs to enable tumor angiogenesis under high lactic acid conditions in tumors remains poorly understood.
Methodology: The metabolomes of TECs and normal endothelial cells (NECs) were analyzed by capillary electrophoresis time-of-flight mass spectrometry.
Due to advancements in nanotechnology, the application of nanosized materials (nanomaterials) in cancer diagnostics and therapeutics has become a leading area in cancer research. The decoration of nanomaterial surfaces with biological ligands is a major strategy for directing the actions of nanomaterials specifically to cancer cells. These ligands can bind to specific receptors on the cell surface and enable nanomaterials to actively target cancer cells.
View Article and Find Full Text PDFRadiotherapy is used extensively in cancer treatment, but radioresistance and the metastatic potential of cancer cells that survive radiation remain critical issues. There is a need for novel treatments to improve radiotherapy. Here, we evaluated the therapeutic benefit of λ-carrageenan (CGN) to enhance the efficacy of radiation treatment and investigated the underlying molecular mechanism.
View Article and Find Full Text PDFEndothelin (ET)-1 is involved in the vascular system, cell proliferation and apoptosis. ET receptors consist of ET type A receptor (ET R) and ET type B receptor (ET R). ET R and ET R generally exhibit opposite responses, although many exceptions exist.
View Article and Find Full Text PDFMitochondria dynamically alter their subcellular localization during cell movement, although the underlying mechanisms remain largely elusive. The small GTPase Arf6 and its signaling pathway involving AMAP1 promote cell invasion via integrin recycling. Here we show that the Arf6-AMAP1 pathway promote the anterograde trafficking of mitochondria.
View Article and Find Full Text PDFRadiotherapy induces anti-tumor immunity by induction of tumor antigens and damage-associated molecular patterns (DAMP). DNA, a representative DAMP in radiotherapy, activates the stimulator of interferon genes (STING) pathway which enhances the immune response. However, the immune response does not always parallel the inflammation associated with radiotherapy.
View Article and Find Full Text PDFGold nanoparticles (AuNPs) have recently attracted attention as clinical agents for enhancing the effect of radiotherapy in various cancers. Although radiotherapy is a standard treatment for cancers, invasive recurrence and metastasis are significant clinical problems. Several studies have suggested that radiation promotes the invasion of cancer cells by activating molecular mechanisms involving integrin and fibronectin (FN).
View Article and Find Full Text PDFHypoxia is a potent microenvironmental factor that promotes tumor metastasis. Recent studies have revealed mechanisms by which hypoxia and activation of hypoxia inducible factor (HIF)-dependent signaling promotes metastasis through the regulation of metabolic reprogramming, the stem cell phenotype, invasion, angiogenesis, immune suppression, the premetastatic niche, intravasation and/or extravasation, and resistance to apoptosis. These discoveries suggest novel paradigms in tumor metastasis and identify new opportunities for therapeutic intervention in the prevention and treatment of metastatic disease.
View Article and Find Full Text PDFRecent studies have revealed that newly emerging transformed cells are often apically extruded from epithelial tissues. During this process, normal epithelial cells can recognize and actively eliminate transformed cells, a process called epithelial defence against cancer (EDAC). Here, we show that mitochondrial membrane potential is diminished in RasV12-transformed cells when they are surrounded by normal cells.
View Article and Find Full Text PDFNik-related kinase (Nrk) is a Ser/Thr kinase and was initially discovered as a molecule that was predominantly detected in skeletal muscles during development. A recent study using Nrk-null mice suggested the importance of Nrk in proper placental development; however, the molecular mechanism remains unknown. In this study, we demonstrated that differentiated trophoblasts from murine embryonic stem cells (ESCs) endogenously expressed Nrk and that Nrk disruption led to the enhanced proliferation of differentiated trophoblasts.
View Article and Find Full Text PDFBackground: Squamous cell carcinoma of the tongue (tongue SCC) is a major subtype of head and neck squamous cell carcinoma (HNSCC), which is an intractable cancer under current therapeutics. ARF6 and its effector AMAP1 are often overexpressed in different types of cancers, such as breast cancer and renal cancer, and in these cancers, AMAP1 binds to EPB41L5 to promote invasion, metastasis, and drug resistance. EPB41L5 is a mesenchymal-specific protein, normally induced during epithelial-mesenchymal transition (EMT) to promote focal adhesion dynamics.
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