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Gene Review

CCL16  -  chemokine (C-C motif) ligand 16

Homo sapiens

Synonyms: C-C motif chemokine 16, CKb12, Chemokine CC-4, Chemokine LEC, HCC-4, ...
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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


Anatomical context of CCL16


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


Other interactions of CCL16


Analytical, diagnostic and therapeutic context of CCL16


  1. Liver-expressed chemokine/CC chemokine ligand 16 attracts eosinophils by interacting with histamine H4 receptor. Nakayama, T., Kato, Y., Hieshima, K., Nagakubo, D., Kunori, Y., Fujisawa, T., Yoshie, O. J. Immunol. (2004) [Pubmed]
  2. Human CC chemokine liver-expressed chemokine/CCL16 is a functional ligand for CCR1, CCR2 and CCR5, and constitutively expressed by hepatocytes. Nomiyama, H., Hieshima, K., Nakayama, T., Sakaguchi, T., Fujisawa, R., Tanase, S., Nishiura, H., Matsuno, K., Takamori, H., Tabira, Y., Yamamoto, T., Miura, R., Yoshie, O. Int. Immunol. (2001) [Pubmed]
  3. Intralesional injection of adenovirus encoding CC chemokine ligand 16 inhibits mammary tumor growth and prevents metastatic-induced death after surgical removal of the treated primary tumor. Guiducci, C., Di Carlo, E., Parenza, M., Hitt, M., Giovarelli, M., Musiani, P., Colombo, M.P. J. Immunol. (2004) [Pubmed]
  4. Differential CCR1-mediated chemotaxis signaling induced by human CC chemokine HCC-4/CCL16 in HOS cells. Kim, I.S., Jang, S.W., Sung, H.J., Lee, J.S., Ko, J. FEBS Lett. (2005) [Pubmed]
  5. Carbohydrate ligands of the LEC cell adhesion molecules. Brandley, B.K., Swiedler, S.J., Robbins, P.W. Cell (1990) [Pubmed]
  6. Clearance of NH2-terminal propeptides of types I and III procollagen is a physiological function of the scavenger receptor in liver endothelial cells. Melkko, J., Hellevik, T., Risteli, L., Risteli, J., Smedsrød, B. J. Exp. Med. (1994) [Pubmed]
  7. Comparison of wild-type and subacute sclerosing panencephalitis strains of measles virus. Neurovirulence in ferrets and biological properties in cell cultures. Thormar, H., Mehta, P.D., Brown, H.R. J. Exp. Med. (1978) [Pubmed]
  8. Reversal of tamoxifen resistance of human breast carcinomas in vivo by neutralizing antibodies to transforming growth factor-beta. Arteaga, C.L., Koli, K.M., Dugger, T.C., Clarke, R. J. Natl. Cancer Inst. (1999) [Pubmed]
  9. MCF7/LCC2: a 4-hydroxytamoxifen resistant human breast cancer variant that retains sensitivity to the steroidal antiestrogen ICI 182,780. Brünner, N., Frandsen, T.L., Holst-Hansen, C., Bei, M., Thompson, E.W., Wakeling, A.E., Lippman, M.E., Clarke, R. Cancer Res. (1993) [Pubmed]
  10. MCF7/LCC9: an antiestrogen-resistant MCF-7 variant in which acquired resistance to the steroidal antiestrogen ICI 182,780 confers an early cross-resistance to the nonsteroidal antiestrogen tamoxifen. Brünner, N., Boysen, B., Jirus, S., Skaar, T.C., Holst-Hansen, C., Lippman, J., Frandsen, T., Spang-Thomsen, M., Fuqua, S.A., Clarke, R. Cancer Res. (1997) [Pubmed]
  11. Steroid metabolism in the hormone dependent MCF-7 human breast carcinoma cell line and its two hormone resistant subpopulations MCF-7/LCC1 and MCF-7/LCC2. Jørgensen, L., Brünner, N., Spang-Thomsen, M., James, M.R., Clarke, R., Dombernowsky, P., Svenstrup, B. J. Steroid Biochem. Mol. Biol. (1997) [Pubmed]
  12. Comparative mechanism and toxicity of tetra- and dithiomolybdates in the removal of copper. Ogra, Y., Komada, Y., Suzuki, K.T. J. Inorg. Biochem. (1999) [Pubmed]
  13. The nuclear factor kappa B inhibitor parthenolide restores ICI 182,780 (Faslodex; fulvestrant)-induced apoptosis in antiestrogen-resistant breast cancer cells. Riggins, R.B., Zwart, A., Nehra, R., Clarke, R. Mol. Cancer Ther. (2005) [Pubmed]
  14. LEC induces chemotaxis and adhesion by interacting with CCR1 and CCR8. Howard, O.M., Dong, H.F., Shirakawa, A.K., Oppenheim, J.J. Blood (2000) [Pubmed]
  15. CC-Chemokine Ligand 16 Induces a Novel Maturation Program in Human Immature Monocyte-Derived Dendritic Cells. Cappello, P., Fraone, T., Barberis, L., Costa, C., Hirsch, E., Elia, A.R., Caorsi, C., Musso, T., Novelli, F., Giovarelli, M. J. Immunol. (2006) [Pubmed]
  16. Isolation and characterization of LMC, a novel lymphocyte and monocyte chemoattractant human CC chemokine, with myelosuppressive activity. Youn, B.S., Zhang, S., Broxmeyer, H.E., Antol, K., Fraser, M.J., Hangoc, G., Kwon, B.S. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  17. Cloning, characterization and genomic organization of LCC-1 (scya16), a novel human CC chemokine expressed in liver. Yang, J.Y., Spanaus, K.S., Widmer, U. Cytokine (2000) [Pubmed]
  18. Estrogen withdrawal-induced NF-kappaB activity and bcl-3 expression in breast cancer cells: roles in growth and hormone independence. Pratt, M.A., Bishop, T.E., White, D., Yasvinski, G., Ménard, M., Niu, M.Y., Clarke, R. Mol. Cell. Biol. (2003) [Pubmed]
  19. Acquisition of hormone-independent growth in MCF-7 cells is accompanied by increased expression of estrogen-regulated genes but without detectable DNA amplifications. Brünner, N., Boulay, V., Fojo, A., Freter, C.E., Lippman, M.E., Clarke, R. Cancer Res. (1993) [Pubmed]
  20. Changes in gap junction organization and decreased coupling during induced apoptosis in lens epithelial and NIH-3T3 cells. Theiss, C., Mazur, A., Meller, K., Mannherz, H.G. Exp. Cell Res. (2007) [Pubmed]
  21. CCL16 activates an angiogenic program in vascular endothelial cells. Strasly, M., Doronzo, G., Capello, P., Valdembri, D., Arese, M., Mitola, S., Moore, P., Alessandri, G., Giovarelli, M., Bussolino, F. Blood (2004) [Pubmed]
  22. Characterization of a novel CC chemokine, HCC-4, whose expression is increased by interleukin-10. Hedrick, J.A., Helms, A., Vicari, A., Zlotnik, A. Blood (1998) [Pubmed]
  23. IL-10 enhances CCL2 release and chemotaxis induced by CCL16 in human monocytes. Musso, T., Cappello, P., Stornello, S., Ravarino, D., Caorsi, C., Otero, K., Novelli, F., Badolato, R., Giovarelli, M. International journal of immunopathology and pharmacology. (2005) [Pubmed]
  24. Genomic organization of the genes for human and mouse CC chemokine LEC. Fukuda, S., Hanano, Y., Iio, M., Miura, R., Yoshie, O., Nomiyama, H. DNA Cell Biol. (1999) [Pubmed]
  25. LEC/chTNT-3 fusion protein for the immunotherapy of experimental solid tumors. Li, J., Hu, P., Khawli, L.A., Epstein, A.L. J. Immunother. (2003) [Pubmed]
  26. 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. Nagano, K., Nakamura, K., Urakami, K.I., Umeyama, K., Uchiyama, H., Koiwai, K., Hattori, S., Yamamoto, T., Matsuda, I., Endo, F. Hepatology (1998) [Pubmed]
  27. Multiprotein complex formation at the beta myosin heavy chain distal muscle CAT element correlates with slow muscle expression but not mechanical overload responsiveness. Vyas, D.R., McCarthy, J.J., Tsika, G.L., Tsika, R.W. J. Biol. Chem. (2001) [Pubmed]
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