Dual role of CCL3/CCR1 in oral squamous cell carcinoma: implications in tumor metastasis and local host defense.
Chemokines are small chemotactic cytokines that can induce the migration of leukocytes, activate inflammatory/immune responses and have recently been implicated in the regulation of tumor growth and organ-specific spread. In this setting, the macrophage inflammatory protein-1alpha (CCL3) chemokine displays a diversity of roles that may contribute to the directional migration of squamous cells into cervical lymph nodes or to the defense against tumor initiation and progression. Thus, the aim of this study was to determine, for the first time, the expression of CCL3 and their receptors, CCR1 and CCR5, by real-time polymerase chain reaction in samples obtained from oral squamous cell carcinoma (OSCC) and healthy gingival tissue (control). In addition, we investigated the immunoexpression of these molecules in neoplastic cells (parenchyma), inflammatory/immune cells (stroma) in primary OSCC and in metastatic and non-metastatic lymph node tissues. The relationship of CCL3/CCR1 with survival data was also evaluated. The analysis of mRNA expression revealed a significantly higher expression of CCL3 and CCR1 in OSCC compared with the controls (P<0.05). The expression of CCR5 was not different in the two groups. The percentages of CCL3+ and CCR1+ cells were observed to be similar in parenchyma and stroma in the OSCC without lymph node metastasis when compared with OSCC with lymph node metastasis (P>0.05). However, we observed the density of CCL3+ nodal cells to be significantly higher in metastatic lymph nodes when compared with non-metastatic lymph nodes in the same patients (P<0.05). Considering CCL3 in stroma, the mean survival rate for patients with high CCL3+ cell percentage was better than for those with low CCL3+ cell percentage. Our findings suggest that the CCL3/CCR1 axis may have a role in the spread of tumoral cells to the lymph nodes and also in the local host defense against the tumor.
Silva
Tarcília Aparecida
TA
Department of Oral Surgery and Pathology, Dental School, Federal University of Minas Gerais, Belo Horizonte, CEP 31270-217, Brazil.
Ribeiro
Fernanda Luiza Leite
FL
Oliveira-Neto
Helenisa Helena de
HH
Watanabe
Satiro
S
Alencar
Rita de Cássia Gonçalves
Rde C
Fukada
Sandra Yasuyo
SY
Cunha
Fernando Queiroz
FQ
Leles
Claudio Rodrigues
CR
Mendonça
Elismauro Francisco
EF
Batista
Aline Carvalho
AC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D016022:Case-Control Studies; D054405:Chemokine CCL3 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054389:Receptors, CCR1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate
C515300:CCR1 protein, human; D054405:Chemokine CCL3; D012333:RNA, Messenger; D054389:Receptors, CCR1