Cell lines:
- Synergistic interaction between
IL-6 and TNF alpha, on the growth inhibition (50% reduction in the percentage of S-phase cells) and the upregulation of ICAM-1 expression (4 to 11-fold increase) was shown in MCF-7 breast cancer cells (BCC) using flow cytometric methods.
IL-6 and TNF alpha alone had negligible effect on the cell cycle. The individual effect of
IL-6 resulted in down-regulation of ICAM-1 expression (30-35%), while TNF alpha always upregulated ICAM-1 (1.5 to 4-fold increase). The combined effect of
IL-6 and TNF alpha consistently caused an increased expression of ICAM-1, which was greater than the sum of each one alone and also sustained for 72 h following cytokine withdrawal (Bajaj P. et al., 1993).
- Four human BCC lines (T47-D, ZR-75-1, MCF-7 and HS578T) were examined for the effects of cytokines on expression of ICAM-1. Interferon-gamma, tumour necrosis factor-alpha,
interleukin (IL)-1 alpha,
IL-1 beta and
IL-6 up-regulated the expression of ICAM-1 in all the BCC lines. Conditioned medium (CM) generated from human fibroblasts, and in particular from foetal cells, was highly effective in up-regulating expression of ICAM-1 in the breast cancer cell lines. ICAM-1 induction correlated with
IL-6 bioactivity in these CMs. Combinations of
IL-6 with other cytokines, such as IL-1, resulted in further increases in ICAM-1 expression (Hutchins D. and Steel C.M., 1994).
- Incubation of SKBR3 BCC with heregulin inhibited anchorage-independent growth while enhancing tyrosine phosphorylation of
c-erbB2. Heregulin treatment also increased adhesion of SKBR3 cells to plastic and increased invasiveness of tumor cells into Matrigel membranes while increasing expression of the
CD44 (HCAM) and
CD54 (ICAM-1) adhesion molecules. Tumor cell invasion of Matrigel membranes was partially blocked by either anti-
CD44 or anti-
CD54 antibodies, indicating a role for these adhesion molecules in the invasion process (Xu F.J. et al., 1997).
-
MUC1 is a ligand for ICAM-1 (Regimbald L.H. et al., 1996). Assays using a murine breast adenocarcinoma cell line transfected with human
MUC1 indicated that the number of
MUC1 tandem repeats necessary for an ordered tertiary structure is important for ICAM-1 recognition (Kam J.L. et al., 1998).
- The phenotypic characteristics of 2 tumor cell lines (BC-H1 and BC-K1) established from bone marrow of patients with breast cancer were studied by immunocytochemistry, flow cytometry, and RT-PCR. Both cell lines expressed
E-cadherin,
vimentin, cytokeratins (including
component 18), alpha 5-,
alpha V-,
beta 1-, and
beta 3- integrin subunits, ICAM-1,
MCAM, LFA-3 (CD58), and
CD44s (but not
CD44v5,
v6,
v7/8). BC-H1 also expressed
ErbB2 (not found in BC-K1), and
MAGE-4 (but not MAGE-1, -2, -3/6, -12; BC-K1 was not tested). The expressed molecules might be potential candidates for novel therapeutic targets (Putz E. et al., 1999).
Tumors:
- ICAM-1 expression was examined in breast cancer by immunohistochemistry. This study included 274 female patients with invasive breast cancer, with a median follow-up of 98 months. The molecule was identified in formalin-fixed, paraffin-embedded primary tumors, and the relationship to clinicopathological factors and prognosis was analyzed. ICAM-1 expression occurred in 50.3% of patients. ICAM-1 expression had negative correlation to tumor size, lymph node metastasis, tumor infiltration, nuclear pleomorphism, and nuclear grade. Patients with ICAM-1-positive tumors had better relapse-free and overall survival than those with negative tumors (Ogawa Y. et al., 1998).
Bajaj P. et al. (1993)
Interleukin-6 and tumour necrosis factor alpha synergistically block S-phase cell cycle and upregulate intercellular adhesion molecule-1 expression on MCF-7 breast carcinoma cells. Cancer Lett. 71, 143-149.
Hutchins D. and Steel C.M. (1994) Regulation of ICAM-1 (CD54) expression in human breast cancer cell lines by
interleukin 6 and fibroblast-derived factors. Int. J. Cancer 58, 80-84.
Kam J.L. et al. (1998)
MUC1 synthetic peptide inhibition of intercellular adhesion molecule-1 and
MUC1 binding requires six tandem repeats. Cancer Res. 58, 5577-5581.
Ogawa Y. et al. (1998) Expression of intercellular adhesion molecule-1 in invasive breast cancer reflects low growth potential, negative lymph node involvement, and good prognosis. Clin. Cancer Res. 4, 31-36.
Putz E. et al. (1999) Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases. Cancer Res. 59, 241-248.
Regimbald L.H. et al. (1996) The breast mucin
MUCI as a novel adhesion ligand for endothelial intercellular adhesion molecule 1 in breast cancer. Cancer Res. 56, 4244-4249.
Staunton D.E. et al. (1988) Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell 52, 925-933.
Tomassini J.E. et al. (1989) cDNA cloning reveals that the major group rhinovirus receptor on HeLa cells is intercellular adhesion molecule 1. Proc. Natl. Acad. Sci. USA 86, 4907-4911.
Voraberger G. et al. (1991) Cloning of the human gene for intercellular adhesion molecule 1 and analysis of its 5'-regulatory region. Induction by cytokines and phorbol ester. J. Immunol. 147, 2777-2786.
Xu F.J. et al. (1997) Heregulin and agonistic anti-
p185(c-erbB2) antibodies inhibit proliferation but increase invasiveness of breast cancer cells that overexpress
p185(c-erbB2): increased invasiveness may contribute to poor prognosis. Clin. Cancer Res. 3, 1629-1634.
