br cells but no or weak
cells, but no or weak expression in surrounding normal lung tissues. Carlsten M et al. [21] detected CD155 overexpression in ovarian cancer cell lines (SKOV-3 and CaOV-4) and cancer Bafilomycin A1 in the ascites of ovarian carcinoma patients. Inozume T et al. [22] found that the CD155 molecule was constitutively expressed in the melanoma cell line (Mel 2) and tumor tissue, while its expression level in nevus cells was very low. Experimental studies performed by Castriconi R1 et al. [23] showed that freshly isolated neuroblastoma cells partially expressed CD155, and its expression level was directly proportional to NK cell-mediated neuroblastoma killing sensitivity. Nishiwada S et al. [10] identified that the CD155 molecule was expressed in non-cancerous tissues (including islet cells), but it was abundantly expressed in the plasma membrane and cytoplasm of pancreatic cancer cells. The prognosis of patients with high CD155 expression was worse than that in patients with low or no CD155 expression. Ochiai H et al. [24] found that the CD155 molecule is almost undetectable in mammary epithelial cell cultures, but its ex-pression is relatively high in BC cell lines (MDA-MB-361, MDA-MB-468,
pression. However, peripheral blood NK cells co-incubated with NK
[26] found that serum concentrations of sCD155 and sMICA/B (soluble
ligands) were higher in colon cancer patients than in healthy donors.
These mechanisms may cause the tumor cells to escape from the anti-
tumor effects of NK or T cells; and in our follow-up studies, whether BC
cells have a similar mechanism needs to be explored.
Our study showed that the expression levels of the CD155 gene and
molecule were related to the primary tumor size, Ki-67, lymph node
overexpression might promote tumor cell proliferation and metastasis.
Tokuyuki Kono et al. [27] transfected the oncogene Ras into NIH3T3
cells to obtain V12Ras-NIH3T3 cells. CD155 expression up-regulated
cyclin D2 and down-regulated p27Kip1, and thus, it shortened the G0/
G1 phase of the cell cycle. CD155 gene silencing induced arrest of the
pancreatic cancer cell lines (MIAPaCa-2 and PANC-1) in the G2/M
phase, and thereby, it inhibited the proliferation of human pancreatic
Necl-5 (CD155) in the bronchioloalveolar carcinoma (BAC) A549 cell
line was higher than that in the lung fibroblast cell line (WI-38). RNA
Fig. 3. The overall survival rate of postoperative patients with BC in the CD155
interference (RNAi) was used to knock down CD155 expression in BAC
high expression group was lower than that in the CD155 low or no expression
cells, and it was observed that CD155 RNAi transfection cells showed
group (P = 0.035).
slow growth and migration, and decreased invasive ability. In sub-
sequent studies, the molecular mechanisms by which CD155 inhibits
MDA-MB-231, and Sk-Br-3). This finding is similar to the results of our
tumor proliferation and promotes invasion and metastasis needs to be
investigated.
study in human BC tissue. We detected the expressions of the CD155
More interestingly, this study also found the CD155 expression level
molecule and gene at different levels (low or no or high expression) in
was significantly associated with CD163/CD8/CD68 expression. It has
fresh BC tissues of 216 patients by IHC and TMA technique.
been reported that TILs are associated with survival of cancer patients.
The above-mentioned phenomenon of high CD155 expression seems
Moreover, TILs also have different immunoregulatory effects towards
to contradict the CD155-CD226-mediated killing effect of NK cells
tumor cells. One of the main functions of CD155 is the immuno-reg-
against tumor cells [25]. Possible reason behind this observation needs
ulatory function in various immune cells. Recent studies have shown
further study. Co-incubation of peripheral blood NK cells from healthy
that CD155 can interact with its ligand T cell’s immune receptor and the
donors with CD155-expressing Drosophila Schneider 2 cell lines
Table 3
Univariate and multivariate analyses of prognostic markers for overall survival in breast cancer.
Univariate analysis
Multivariate analysis
Age (years)
Menopause
Histology grade
ER status
PR status
HER2 status
Tumor size
Lymph node metastasis
TNM
I vs II vs III
Negative vs Positive
Negative vs Positive
Negative vs Positive
immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain in T nuclear and NK cells to produce direct inhibitory effects on cell proliferation and cytotoxicity. On the contrary, CD155 also binds to the DNAX attachment adhesion molecule (DNAM-1)/CD226 on T cells and NK cells, and conversely enhances the cytotoxic function. These results suggest that the immune function of CD155 is complex and its function may be dependent on the interstitial environment [21,29,30].