The CC chemokine RANTES as a potential contributor to breast cancer progression

Abstract

Background: Disruption of the balance between apoptosis and proliferation is considered to be an important factor in the development and progression of tumor. In this study we determined the in vivo cell kinetics along the spectrum of apparently normal epithelium, hyperplasia, preinvasive lesions and invasive carcinoma, in breast tissues affected by fibrocystic changes in which preinvasive and/or invasive lesions developed, as a model of breast carcinogenesis. Materials and method: A total of 32 areas of apparently normal epithelium and 135 ductal proliferative and neoplastic lesions were studied. More than one epithelial lesion per case was analyzed. The apoptotic index (AI) and the proliferative index (PI) were expressed as the percentage of TUNEL (TdT-mediated dUTP-nick end-labelling) and Ki-67 positive cells, respectively. The proliferative/apoptotic index (P/A) was calculated for each case. Results: Statistical analysis demonstrated significant differences among the tissue groups for both indices (P < 0.0001). The Als and PIs were significantly higher in hyperplasia than in apparently normal epithelium (P = 0.04 and P = 0.0005, respectively), in atypical hyperplasia than in hyperplasia (P = 0.01 and P = 0.04, respectively) and in invasive carcinoma than in in situ carcinoma (P = 0.0001 and P < 0.0001, respectively). The two indices were similar in atypical hyperplasia and in in situ carcinoma. The P/A index increased significantly from normal epithelium to hyperplasia (P = 0.01) and from preinvasive lesions to invasive carcinoma (P = 0.04), whereas it was decreased (NS) from hyperplasia to preinvasive lesions. A strong positive correlation between the Als and the Pls was found (r = 0.83; P < 0.0001). Conclusion: These findings suggest accelerating cell turnover along the continuum of breast carcinogenesis. Atypical hyperplasias and in situ carcinomas might be kinetically similar lesions. In the transition from normal epithelium to hyperplasia and from preinvasive lesions to invasive carcinoma, the net growth of epithelial cells results from a growth imbalance in favour of proliferation. In the transition from hyperplasia to preinvasive lesions there is an imbalance in favour of apoptosis.

Tumor-secreted PGE2 Inhibits CCL5 Production in Activated Macrophages through cAMP/PKA Signaling Pathway

“…2, C and D). Consistent with previous reports that breast tumor cells secrete CCL5 (27,28,(42)(43)(44), our data show that 4T1 conditioned medium contained large amounts of CCL5 and this tumor-derived CCL5 did not mediate the inhibition of host CCL5 expression (Fig. 2, G-I).…”

A dual role for tumor-derived chemokine RANTES (CCL5)

“…In addition, the levels of CCL5 expression were greater than that found in normal epithelial cells, ductal epithelial cells and benign sections. A subsequent study by the same group suggested that the expression of matrix metalloproteinase-9 (MMP9) may be regulated by CCL5, and therefore, CCL5 may play a role in invasion and metastases [3]. Why this chemokine, which is capable of recruiting T cells, did not increase the immunogenicity of these tumors remains unanswered.…”

The Lupane-type Triterpene 30-Oxo-calenduladiol Is a CCR5 Antagonist with Anti-HIV-1 and Anti-chemotactic Activities

“…Considering all the presented data, we suggest that 30-oxocalenduladiol is a new and specific CCR5 antagonist that exhibits great promise as a bioactive agent for the development of new high active derivatives for treatment of HIV-1 infection, and against biological disorders related to CCR5-mediated cell migration, such as for instance, inflammation, immune response, and tumor cell migration (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57).…”