Disease relevance of CCL16

• In this study, we demonstrated that CCL16 induced pertussis toxin-sensitive calcium mobilization and chemotaxis in murine L1.2 cells expressing H4 but not those expressing histamine receptor type 1 (H1) or type 2 (H2) [1].
• In spite of its binding to CCR5, LEC was unable to inhibit infection of an R5-type HIV-1 to activated human peripheral blood mononuclear cells even at high concentrations [2].
• An adenovirus encoding CCL16 (AdCCL16) was generated using a Cre-Lox-based system and was used to determine whether this chemokine might also block pre-existing tumors [3].
• Although no murine homologous has been defined, the TSA mouse adenocarcinoma cells engineered to express human CCL16 are rapidly rejected by syngenic mice [3].
• Human osteogenic sarcoma cells stably expressing CCR1 were used to investigate HCC-4-mediated chemotaxis signaling events via CCR1 [4].

High impact information on CCL16

• Carbohydrate ligands of the LEC cell adhesion molecules [5].
• The major site of uptake was the liver, 78, 1, and 21% of its radioactivity being recovered in isolated liver endothelial cells (LEC), Kupffer cells, and parenchymal cells, respectively [6].
• SSPE strains LEC, IP-3, Biken, and D.R., on the other hand, were mostly cell-associated in Vero and FB cultures, although atypical cell-free particles were produced by strains Biken and IP-3 [7].
• SSPE strains LEC, IP-3, Biken, and D.R., on the other hand, were all neurovirulent in ferrets, particularly strain D.R. which caused an acute encephalitis in all inoculated animals [7].
• METHODS: TGF-beta2 expression was evaluated in LCC2 cells and tamoxifen-sensitive LCC1 cells by northern blot analysis [8].

Chemical compound and disease context of CCL16

• A stepwise in vitro selection of the hormone-independent human breast cancer variant MCF-7/LCC1 against 4-hydroxytamoxifen produced a stable resistant population designated MCF7/LCC2 [9].
• We have shown previously that estrogen-independent and -responsive MCF7/LCC1 human breast cancer cells selected for resistance to the triphenylethylene tamoxifen produce a variant (MCF7/LCC2) that retains sensitivity to the steroidal antiestrogen ICI 182,780 (N. Brunner et al., Cancer Res., 53: 3229-3232, 1993) [10].
• Androgen and estrogen metabolism was investigated in the hormone-dependent human breast cancer cell line MCF-7 and its two hormone-resistant sublines MCF-7/LCC1 and MCF-7/LCC2 [11].
• Tetrathiomolybdate (TTM) can be used as a specific chelator to remove copper (Cu) accumulating in the form bound to metallothionein (MT) in the livers of Wilson disease patients and Long-Evans rats with a cinnamon-like coat color (LEC rats) [12].
• Basal expression of multiple NFkappaB-related molecules in MCF7-derived LCC1 (antiestrogen-sensitive) and LCC9 (antiestrogen-resistant) breast cancer cells was determined, and cells were treated with Faslodex or parthenolide [13].

Biological context of CCL16

• This study suggests that LEC may be a more effective inducer of cell adhesion than cell migration [14].
• In the present study, we report that CCL16 is a potent maturation factor for monocyte-derived DCs (MoDCs) through differential use of its four receptors and an indirect regulator of Th cell differentiation [15].
• Although HCC-4 binds to multiple CC chemokine receptors, the receptor-mediated signal transduction pathway induced by HCC-4 has not been characterized [4].
• This data suggests that the LMC gene is located at human chromosome 17q which encompasses a human CC chemokine gene cluster [16].
• The EST for LCC-1 has been previously mapped to the CC chemokine cluster on human chromosome 17q11 [17].

Anatomical context of CCL16

• Intravenous injection of CCL16 into mice induced a rapid mobilization of eosinophils from bone marrow to peripheral blood, which was also suppressed by thioperamide [1].
• Accordingly, CCL16 induced efficient migratory responses in human and mouse eosinophils [1].
• Previously, LEC was shown to induce leukocyte migration but the responsible signaling receptors were not characterized [14].
• HepG2, a human hepatocarcinoma cell line, was found to constitutively express LEC [2].
• In human liver sections, hepatocytes were strongly stained by anti-LEC antibody [2].

Associations of CCL16 with chemical compounds

• SB202190 inhibited HCC-4-induced chemotaxis in a dose-dependent manner (P < 0.01) [4].
• Finally, LCC1 tumors were markedly more sensitive to tamoxifen in NK-active than in NK-deficient mice [8].
• Whereas LCC1 tumors in nude mice were stable or grew, LCC1(IkappaBalpha) tumors regressed after E2 withdrawal [18].
• In the absence of estrogen, steady-state levels of phosphoinositol turnover are similar in both MCF-7 and MCF7/LCC1 cells, but turnover is increased by estrogen only in MCF-7 cells [19].
• Cell coupling at single cell level was tested by direct microinjecting into LEC apoptosis-inducing agents of low molecular mass like staurosporine, etoposide and puromycin or the high molecular mass proteins caspase-3 and -8 in activated state [20].

Regulatory relationships of CCL16

• Here we report that CCL16 activates an angiogenic program in vascular endothelial cells by activating CCR1 [21].
• HCC-4 also induced a Ca2+ flux in THP-1 cells that was desensitized by prior exposure to RANTES [22].
• HCC-4 induces p38 activation in both a time and dose-dependent manner [4].

Other interactions of CCL16

• The binding of LEC to CCR8 was much less significant [2].
• Liver-expressed chemokine (LEC)/CCL16 is a human CC chemokine selectively expressed in the liver [2].
• CCL16 may be specifically cross-linked to CCR1 expressed on endothelial cells [21].
• IL-10 enhances CCL2 release and chemotaxis induced by CCL16 in human monocytes [23].
• The coordinated secretion of CCL16 and IL-10 may thus enhance monocyte infiltration [23].

Analytical, diagnostic and therapeutic context of CCL16

• Northern blot analysis from a panel of human tissues revealed that LCC-1 mRNA expression is restricted to adult and fetal liver [17].
• Southern blot analysis revealed that the sequence isolated from the BAC clone was the only one hybridizing with human LEC cDNA in the mouse genome [24].
• LEC/chTNT-3 fusion protein for the immunotherapy of experimental solid tumors [25].
• Intracellular distribution of the Wilson's disease gene product (ATPase7B) after in vitro and in vivo exogenous expression in hepatocytes from the LEC rat, an animal model of Wilson's disease [26].
• Electrophoretic mobility shift assay revealed the formation of a specific low migrating nuclear protein complex (LMC) at the betaMyHC MCAT element that was highly enriched only when using either MOV plantaris or control soleus nuclear extract [27].

References