Browsing by Subject "CXCL12"

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    Expression of CXCL12 in esophageal high grade dysplasia characterized pathologically by lymphocyte accumulation directly under the lesion
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Mochizuki, Kunio; Oishi, Naoki; Odate, Toru; Tahara, Ippei; Inoue, Tomohiro; Kasai, Kazunari; Kondo, Tetsuo
    Squamous dysplasia of the esophagus is an unequivocal neoplastic alteration of the esophageal squamous epithelium without invasion. Esophageal high grade dysplasia (EHGD) is characterized by >50% epithelial involvement or severe cytological atypia. Frequently, lymphocytes accumulate below EHGD lesions even though there is no invasion. If this lymphocytic accumulation is active, a transmitter should exist between the EHGD cells and the lymphocytes. CX-C motif chemokine ligand (CXCL) 12, CXCL10 and C-C motif chemokine ligand 18 (CCL18) are all lymphocyte chemoattractants in vivo, but there are no reports on the relationship between these chemokines and EHGDs. In this study, we investigated these chemokines and C-X-C motif chemokine receptor 4 (CXCR4) (receptor for CXCL12) in 30 EHGDs using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). For comparison, we enrolled 30 samples of normal esophageal squamous epithelium (NESE). We confirmed CXCL12 expression (H-score≥50 points) in 70% of EHGD and 0% of NESE samples, CXCL10 expression in 3% of EHGD and 3% of NESE samples, CCL18 expression in 3% of EHGD and 0% of NESE samples, and CXCR4 expression in 53% of EHGD and 0% of NESE samples by immunohistochemistry. EHGD and NESE cases were significantly different in their expressions between the tissue types (CXCL12, p<0.001; CXCR4, p<0.001). We examined CXCL12 and CXCR4 mRNA expressions of 3 representative EHGD samples, each having their respective immunostained areas detected by RT-PCR. Finding CXCL12 expression may indicate that this chemokine plays a part in the lymphocyte accumulation that occurs directly under EHGDs.
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    Expressions of CXCL12, CXCL10 and CCL18 in Warthin tumors characterized pathologically by having a lymphoid stroma with germinal centers
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Mochizuki, Kunio; Oishi, Naoki; Masataka Kawai, Masataka Kawai; Odate, Toru; Tahara, Ippei; Kasai, Kazunari; Kondo, Tetsuo
    The Warthin tumor is a benign neoplasm of the salivary glands, histologically, the tumor has an oncocytic epithelial component forming uniform rows of cells surrounded by cystic spaces associated with a lymphoid stroma often showing the presence of germinal centers. The lymphoid stroma is a representative microscopic finding. If this lymphocytic accumulation is active, some sort of transmitter should exist between the Warthin tumor cells and lymphocytes. C-X-C motif chemokine ligand (CXCL) 12, CXCL10 and C-C motif chemokine ligand 18 (CCL18) are a chemoattractant for lymphocytes in vivo. There is no report on the relationship between these chemokines and Warthin tumors. In this study, we investigated these chemokines expressions in 20 Warthin tumors using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). For comparison, we also enrolled samples of pleomorphic adenoma, which is another benign salivary gland tumor type without prominent lymphocytic infiltration. All Warthin tumors were immunopositive for CXCL12 and CXCL10, and these reactivities were diffuse. Meanwhile, the majority of pleomorphic adenomas were immunonegative for CXCL12 (95%), CXCL10 (80%) and CCL18 (85%). Warthin tumor and pleomorphic adenoma cases were significantly different in these immunostaining expressions (CXCL12, p<0.001; CXCL10, p<0.001; CCL18, p=0.024). We examined CXCL12, CXCL10 and CCL18 mRNA expressions of 3 representative Warthin tumor samples, each having these chemokines immunopositive areas detected by RT-PCR. Finding CXCL12 and CXCL10 expressions indicate that these chemokines may play a part in the formation of a lymphoid stroma within Warthin tumors. In regards to this phenomenon, the participation of CCL18 might be restrictive compared to CXCL12 and CXCL10.
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    The CXCR4/CXCL12 axis in cutaneous malignancies with an emphasis on melanoma
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Mitchell, B.; Mahalingam, Meera
    The highly metastatic and variable behavior of melanoma has accentuated the need for early detection and targeted therapy. Putative targets identified include those belonging to the extensive network of chemokines and their receptors. One such target is the chemokine receptor CXCR4, a G protein-coupled receptor with a 34 amino acid extracellular N-terminus, the primary ligand of which is CXCL12 (SDF-1, stromal derived factor-1). The ligand uniquely utilizes the Nterminus of CXCR4 for signal transduction and stimulates the protein kinase B (AKT)/mitogen activated protein kinase (MAPK) pathway. Functionally, the CXCR4/CXCL12 axis is believed to play a key role in cell migration and proliferation. Upregulation of CXCR4 and consequently dysregulation of the CXCR4/CXCL12 axis has been implicated in the progression of several lineage-unrelated malignancies including melanoma. The contributions of the CXCR4/CXCL12 axis in melanomagenesis are well documented. More recently, the potential cooperativity between the mutational status of BRAF and the CXCR4/CXCL12 axis has been shown, lending credence to the concept that both CXCR4 and CXCL12 may be putative targets for therapy in melanoma. In this review, we summarize the role of the CXCR4/CXCL12 axis in cancer progression and metastasis, with an emphasis on cutaneous malignancy, melanoma in particular. Furthermore, we discuss the effects of CXCL12 on CXCR4 expressing malignant cells in vitro and the potential prognostic utility of both CXCR4 and CXCL12 expressions. Lastly, we highlight the therapeutic potential of targeting this axis and the unique response of CXCR4 expression to anti-cancer treatments with an emphasis on melanoma.