Search

Human head and neck cancer (HNC) is a highly heterogeneous disease. Understanding the biology of HNC progression is necessary for the development of novel approaches to its prevention, early detection, and treatment. A current evolutional progression model has limitations in explaining the heterogeneity observed in a single tumor nest. Accumulating evidence supports the existence of cancer stem cells (CSCs) as small subpopulations in solid tumors, including HNC. These CSCs can be selected by appropriate cell surface markers, which are cancer type specific and have been confirmed by unique in vitro and in vivo assays. Selected CSC populations maintain a self-renewal capability and show aggressive behaviors, such as chemoresistance and metastasis. In addition to introducing the CSC concept in solid tumors, this short review summarizes current publications in HNC CSC and the prospective development and application of the CSC concept to HNC in the clinic. [ABSTRACT FROM AUTHOR]

Side Population (SP) cells, a subset of Hoechst-low cells, are enriched with stem cells. Originally, SP cells were isolated from bone marrow but recently have been found in various solid tumors and cancer cell lines that are clonogenic in vitro and tumorigenic in vivo. In this study, SP cells from lymph node metastatic head and neck squamous cell carcinoma (HNSCC) cell lines were examined using flow cytometry and Hoechst 3342 efflux assay. We found that highly metastatic HNSCC cell lines M3a2 and M4e contained more SP cells compared to the low metastatic parental HNSCC cell line 686LN. SP cells in HNSCC were highly invasive in vitro and tumorigenic in vivo compared to non-SP cells. Furthermore, SP cells highly expressed ABCG2 and were chemoresistant to Bortezomib and etoposide. Importantly, we found that SP cells in HNSCC had abnormal activation of Wnt/b-catenin signaling as compared to non-SP cells. Together, these findings indicate that SP cells might be a major driving force of head and neck tumor formation and metastasis. The Wnt/b-catenin signaling pathway may be an important target for eliminating cancer stem cells in HNSCC. [ABSTRACT FROM AUTHOR]

Here, we report photodynamic oncotherapies mediated by gonadotropin-releasing hormone (GnRH) receptors. We synthesized conjugates 1 and 2 by coupling zinc phthalocyanine (ZnPc) to GnRH analogues. Compared to unmodified ZnPc, conjugates 1 and 2 exhibited higher and more specific phototoxicities to breast cancer cells. Furthermore, the two conjugates demonstrated excellent antitumor efficacies in a breast cancer-grafted animal model. Biodistribution study suggested the high biosafety of conjugate 2 because of the low retention in brain and skin. [ABSTRACT FROM AUTHOR]

Sulfhydryl-containing proteins play critical roles in various physiological and biological processes, and the activities of those proteins have been reported to be susceptible to thiol oxidation. Therefore, the development of protein thiol target fluorescent probe is highly desirable. In the present work, a biotinylated coumarin fluorescence "off-on" probe SQ for selectively detecting protein thiols in biotin receptor-positive cancer cells was designed with a 2,4-dinitrobenzenesulfony as the thiol receptor. The probe exhibited dramatic fluorescence responses toward sulfhydryl-containing proteins (ovalbumin (OVA), bovine serum albumin (BSA)): up to 170-fold fluorescence enhancement with 70 nm blue-shift was observed with the addition of OVA. However, low molecular weight thiols (Cys, glutathione (GSH), Hey) caused negligible fluorescence changes of SQ In addition, biotin receptor-positive Hela cells displayed strong red and green fluorescence after incubation of SQfor 1 h; neither red nor green fluorescence signal could be visualized in biotin-negative normal lung Wi38 cells. These results imply that the probe has potential application in fluorescent imaging protein thiols on the surface of Hela cells. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS), also known as osteogenic sarcoma, is the most common primary malignancy of bone tumor in children and adolescents. However, its underlying molecular pathogenesis is still only vaguely understood. Recently, LIM mineralization protein-1 (LMP-1) was reported to be an essential positive regulator of osteoblast differentiation. In the present study, we found that the expression of LMP-1 is downregulated in OS tissues compared with adjacent normal tissues. Moreover, we restored the expression of LMP-1 through a recombinant adenovirus. Overexpression of LMP-1 inhibited cell proliferation and invasion, arrested cell cycle progression, and induced apoptosis in vitro. Finally, ectopic LMP-1 expression suppressed the expression of Runx2 and BMP-2 in OS cells. These data demonstrate that LMP-1 is an essential tumor suppressor in the OS pathological process, which will provide a new opportunity for discovering and identifying novel effective treatment strategies. [ABSTRACT FROM AUTHOR]

Chemokine receptor 7 (CCR7) upregulation, which mediates immune cell survival and migration to lymph nodes, has recently been associated with nodal metastasis of squamous cell carcinoma of the head and neck (SCCHN). However, the mechanism of CCR7 in tumor progression, its downstream signaling mediators, and interactions with other pathways contributing to metastasis of SCCHN have not been determined. We hypothesized that inflammatory chemokine-mediated signals could also promote tumor proliferation and mitogenic effects. Functional assays showed that chemotaxis and invasion of metastatic SCCHN cells were dependent on phosphoinositide-3 kinase (PI3K) and its substrate, activated phospholipase Cγ-1. In addition, treatment of CCR7+ metastatic SCCHN cells with CCL19 (MIP-3β) showed rapid activation of the prosurvival, PI3K/Akt pathway. Transactivation of EGFR-mediated and mitogen-activated protein kinase signaling pathways, which can promote migration and survival in parallel, did not appear to contribute to the functional or biochemical effects of CCR7 stimulation. Thus, proinflammatory chemokine signals that mediate activation, trafficking and survival of tumor-infiltrating immune cells in the tumor microenvironment actually appear to induce signals for progression of cancer cells. The CCR7-mediated pathway in metastatic SCCHN cells functions independently of EGFR signal transduction and therefore may represent an additional target for therapeutic intervention to prevent tumor progression and metastasis.Oncogene (2005) 24, 5897–5904. doi:10.1038/sj.onc.1208740; published online 13 June 2005 [ABSTRACT FROM AUTHOR]