scholarly journals Melanocyte and Melanoma Cell Activation by Calprotectin

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Stephanie H. Shirley ◽  
Kristine von Maltzan ◽  
Paige O. Robbins ◽  
Donna F. Kusewitt
Keyword(s):  
Ultraviolet Radiation ◽  
Cell Activation ◽  
Melanoma Cells ◽  
Target Cells ◽  
Paracrine Factors ◽  
Matrigel Invasion ◽  
Human Melanocytes ◽  
End Products ◽  
Normal Human

Calprotectin, a heterodimer of S100A8 and S100A9, is a proinflammatory cytokine released from ultraviolet radiation-exposed keratinocytes. Calprotectin binds to Toll-like receptor 4, the receptor for advanced glycation end-products, and extracellular matrix metalloproteinase inducer on target cells to stimulate migration. Melanocytes and melanoma cells produce little if any calprotectin, but they do express receptors for the cytokine. Thus, keratinocyte-derived calprotectin has the potential to activate melanocytes and melanoma cells within the epidermis in a paracrine manner. We examined the ability of calprotectin to stimulate proliferation and migration in normal human melanocytes and melanoma cellsin vitro. We first showed, by immunofluorescence and quantitative RT-PCR, that the melanocytic cells employed expressed a calprotectin receptor, the receptor for advanced end-products. We then demonstrated that calprotectin significantly enhanced proliferation, migration, and Matrigel invasion in both normal human melanocytes and melanoma cells. Thus, calprotectin is one of the numerous paracrine factors released by ultraviolet radiation-exposed keratinocytes that may promote melanomagenesis and is a potential target for melanoma prevention or therapy.

E-cadherin is the major mediator of human melanocyte adhesion to keratinocytes in vitro

1994 ◽  
Vol 107 (4) ◽  
pp. 983-992 ◽  
Author(s):  
A. Tang ◽  
M.S. Eller ◽  
M. Hara ◽  
M. Yaar ◽  
S. Hirohashi ◽  
...  
Keyword(s):  
Cell Types ◽  
Melanoma Metastasis ◽  
Normal Keratinocytes ◽  
Human Melanocyte ◽  
Human Melanocytes ◽  
Dependent Cell ◽  
Normal Human ◽  
Pre Treatment ◽  
E Cadherin

E- and P-cadherin are calcium (Ca2+)-dependent cell adhesion molecules important in the morphogenesis and maintenance of skin structure. By use of flow cytometry and specific antibodies, we now show that cultured human melanocytes express E- and P-cadherin on their surfaces, and that these molecules have the same characteristics as reported for other cell types. Specifically, melanocyte cadherins are sensitive to trypsin digestion in the absence of Ca2+ and are protected from trypsin degradation by Ca2+, and are functional at 37 degrees C but not at 4 degrees C. We further show that melanocytes contain mRNA transcripts encoding both E- and P-cadherin. Adhesion of cultured melanocytes to keratinocyte monolayers is abolished by pre-treatment of the melanocytes with trypsin/EDTA, which degrades E- and P-cadherins, is greatly reduced by anti-E-cadherin antibodies and is slightly reduced by antibodies to P-cadherin, alpha 2, alpha 3 and beta 1 integrins. In contrast to normal melanocytes, eight of nine melanoma cell lines lacked E-cadherin (or expressed markedly reduced levels) and five were negative for P-cadherin. Melanoma cells also failed to adhere to keratinocyte monolayers. These results demonstrate that normal human melanocytes express functional E- and P-cadherin and that E-cadherin is primarily responsible for adhesion of human melanocytes to keratinocytes in vitro. In addition, transformed melanocytes express markedly reduced levels of E- and P-cadherin, and exhibit decreased affinity for normal keratinocytes in vitro, suggesting that loss of cadherins may play a role in melanoma metastasis.

scholarly journals CD18 Antibody Application Blocks Unwanted Off-Target T Cell Activation Caused by Bispecific Antibodies

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4596
Author(s):  
Joseph Kauer ◽  
Fabian Vogt ◽  
Ilona Hagelstein ◽  
Sebastian Hörner ◽  
Melanie Märklin ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphoid Cells ◽  
Bispecific Antibodies ◽  
Target Cells ◽  
Cytokine Release ◽  
Life Threatening ◽  
Blocking Antibodies

T cell-recruiting bispecific antibodies (bsAbs) are successfully used for the treatment of cancer. However, effective treatment with bsAbs is so far hampered by severe side effects, i.e., potentially life-threatening cytokine release syndrome. Off-target T cell activation due to binding of bispecific CD3 antibodies to T cells in the absence of target cells may contribute to excessive cytokine release. We report here, in an in vitro setting, that off-target T cell activation is induced by bsAbs with high CD3 binding affinity and increased by endothelial- or lymphoid cells that act as stimulating bystander cells. Blocking antibodies directed against the adhesion molecules CD18/CD54 or CD2/CD58 markedly reduced this type of off-target T cell activation. CD18 blockade—in contrast to CD2—did not affect the therapeutic activity of various bsAbs. Since CD18 antibodies have been shown to be safely applicable in patients, blockade of this integrin holds promise as a potential target for the prevention of unwanted off-target T cell activation and allows the application of truly effective bsAb doses.

Stimulatory Effect of Prostaglandin E2 on the Configuration of Normal Human Melanocytes In Vitro

1987 ◽  
Vol 89 (3) ◽  
pp. 299-301 ◽  
Author(s):  
Yasushi Tomita ◽  
Masatoshi Iwamoto ◽  
Takayuki Masuda ◽  
Hachiro Tagami
Keyword(s):  
Prostaglandin E2 ◽  
Human Melanocytes ◽  
Normal Human

scholarly journals 1,25-dihydroxyvitamin D3 differentiates normal neutrophilic promyelocytes to monocytes/macrophages in vitro

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2693-2701 ◽  
Author(s):  
K Nakamura ◽  
T Takahashi ◽  
Y Sasaki ◽  
R Tsuyuoka ◽  
Y Okuno ◽  
...  
Keyword(s):  
Target Cells ◽  
Essential Factor ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Morphological Evaluation ◽  
Secondary Culture ◽  
Normal Human ◽  
The Individual ◽  
Stimulating Factor

Although it is well established that the addition of 1,25- dihydroxyvitamin D3 (D3) to the culture of normal human granulocyte/macrophage progenitors induces monocyte/macrophage (Mo/M phi) colonies, the target cells of D3 in the Mo/M phi differentiation have not been identified. We examined whether neutrophilic promyelocytes are the target cells. As a source of the promyelocyte fraction, we used colonies after 5 days of culture (5-day colonies) of colony-forming unit-granulocyte. The culture contained granulocyte colony-stimulating factor (G-CSF) as the growth factor and generated only neutrophilic colonies. The promyelocytic nature of the 5-day colonies was confirmed morphologically, cytochemically, and ultrastructurally. After morphological evaluation on part of the individual colonies, they were transferred into new semisolid cultures with or without D3 (10(-7) mol/L) in the presence of G-CSF, then incubated for the subsequent 7 days. With D3, the colonies were loose, and all the constituent cells were morphologically small macrophages, which were positive for alpha-naphthyl butyrate (alpha NB) esterase, strongly positive for CD14 antigen, and plastic-adherent. While without D3, the colonies were rather compact, and all the constituent cells were morphologically mature neutrophils, which were positive for naphthol ASD-chloroacetate esterase and weakly positive for CD14 antigen. Secondary culture of the 8- or 10-day colonies with D3 induced a lower number of alpha NB-positive cells, in proportion to the percentage of promyelocytes at the time of transfer in each colony. Four days of secondary culture with D3 was sufficient to induce alpha NB-positive cells. G-CSF was not an essential factor to induce alpha NB- positive cells. These findings indicate that D3 differentiates normal human neutrophilic promyelocytes into the Mo/M phi lineage in vitro.

scholarly journals Oligonucleotide uptake in human hematopoietic cells is increased in leukemia and is related to cellular activation

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1788-1795 ◽  
Author(s):  
Q Zhao ◽  
X Song ◽  
T Waldschmidt ◽  
E Fisher ◽  
AM Krieg
Keyword(s):  
T Cells ◽  
Cell Activation ◽  
Hematopoietic Cells ◽  
Leukemic Cells ◽  
Cellular Activation ◽  
Therapeutic Drugs ◽  
Normal Human ◽  
Novel Strategy

Abstract The use of antisense oligonucleotides as tools for modulating gene expression represents a novel strategy for designing drugs to treat a variety of diseases. Several factors, including cellular uptake and internalization of the oligonucleotides, are important parameters in determining the effectiveness of antisense agents such as therapeutic drugs. We have studied oligonucleotides uptake in normal and leukemic human hematopoietic cells, such as peripheral blood, bone marrow (BM), and HL-60 cell line; and have found that, in normal human blood and BM, myeloid cells and B cells preferably took up more oligonucleotides than T cells. There was no marked difference in oligonucleotide uptake between CD4+ helper T cells and CD8+ cytolytic T cells. Leukemic cells had greater oligonucleotide uptake than their normal counterparts. Furthermore, oligonucleotide uptake was closely related to cell activation status and can be modulated by growth factors or inhibitors. These studies provide a basis for using oligonucleotides as therapeutic drugs both in vitro and in vivo.

Quercetin Enhances Melanogenesis By Increasing the Activity and Synthesis of Tyrosinase in Human Melanoma Cells and in Normal Human Melanocytes

2004 ◽  
Vol 17 (1) ◽  
pp. 66-73 ◽  
Author(s):  
Hidetaka Nagata ◽  
Susumu Takekoshi ◽  
Reiko Takeyama ◽  
Takao Homma ◽  
R. Yoshiyuki Osamura
Keyword(s):  
Melanoma Cells ◽  
Human Melanoma ◽  
Human Melanoma Cells ◽  
Human Melanocytes ◽  
Normal Human
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