CXCL12 expression by healthy and malignant ovarian epithelial cells.

CXCL12 expression by healthy and malignant ovarian epithelial cells.
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DOI:
10.1186/1471-2407-11-97
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发表时间:
2011-03-16
期刊:
影响因子:
3.8
通讯作者:
Balabanian K
Balabanian K
中科院分区:
医学2区
文献类型:
--
作者:
Machelon V;Gaudin F;Camilleri-Broët S;Nasreddine S;Bouchet-Delbos L;Pujade-Lauraine E;Alexandre J;Gladieff L;Arenzana-Seisdedos F;Emilie D;Prévot S;Broët P;Balabanian K

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CXCL 12已被广泛报道在肿瘤生长和扩散中发挥生物学相关作用。在上皮性卵巢癌(EOC)中,CXCL 12增强肿瘤血管生成并有助于免疫抑制网络。然而,其预后意义仍不清楚。因此,我们比较了健康和恶性卵巢中CXCL 12的状态,以评估其预后价值。免疫组织化学用于分析CXCL 12在生殖道中的表达,包括健康女性的卵巢和输卵管、良性和交界性上皮肿瘤以及来自晚期原发性EOC患者的一系列183个肿瘤标本,这些患者参加了紫杉醇/卡铂/吉西他滨化疗的多中心前瞻性临床试验(GINECO研究)。单因素考克斯模型分析临床和生物学变量的预后价值。Kaplan-Meier方法用于生成无进展和总生存曲线。卵巢和输卵管表面的上皮细胞对CXCL 12染色呈阳性,而卵巢内的卵泡没有。良性、交界性和恶性肿瘤的上皮细胞也表达CXCL 12。在上皮性卵巢癌标本中,CXCL 12免疫反应主要见于上皮性肿瘤细胞。86例(47%)信号较强,18例(<10%)信号消失。CXCL 12的这种不均匀分布并不能反映EOC的形态学异质性。CXCL 12表达水平与目前用于确定EOC预后的任何临床参数或与HER 2状态无关。它们对无进展生存期或总生存期也没有影响。我们的研究结果突出了以前未被重视的组成型表达的CXCL 12的卵巢表面和输卵管的健康上皮细胞,表明EOC可能起源于这些上皮细胞。我们发现恶性上皮细胞产生CXCL 12先于肿瘤发生,并且我们在一个大型的晚期EOC患者队列中证实,EOC中CXCL 12表达水平本身不是一个有价值的预后因素。ClinicalTrials.gov:NCT00052468
CXCL12 has been widely reported to play a biologically relevant role in tumor growth and spread. In epithelial ovarian cancer (EOC), CXCL12 enhances tumor angiogenesis and contributes to the immunosuppressive network. However, its prognostic significance remains unclear. We thus compared CXCL12 status in healthy and malignant ovaries, to assess its prognostic value. Immunohistochemistry was used to analyze CXCL12 expression in the reproductive tracts, including the ovaries and fallopian tubes, of healthy women, in benign and borderline epithelial tumors, and in a series of 183 tumor specimens from patients with advanced primary EOC enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin/gemcitabine-based chemotherapy (GINECO study). Univariate COX model analysis was performed to assess the prognostic value of clinical and biological variables. Kaplan-Meier methods were used to generate progression-free and overall survival curves. Epithelial cells from the surface of the ovary and the fallopian tubes stained positive for CXCL12, whereas the follicles within the ovary did not. Epithelial cells in benign, borderline and malignant tumors also expressed CXCL12. In EOC specimens, CXCL12 immunoreactivity was observed mostly in epithelial tumor cells. The intensity of the signal obtained ranged from strong in 86 cases (47%) to absent in 18 cases (<10%). This uneven distribution of CXCL12 did not reflect the morphological heterogeneity of EOC. CXCL12 expression levels were not correlated with any of the clinical parameters currently used to determine EOC prognosis or with HER2 status. They also had no impact on progression-free or overall survival. Our findings highlight the previously unappreciated constitutive expression of CXCL12 on healthy epithelia of the ovary surface and fallopian tubes, indicating that EOC may originate from either of these epithelia. We reveal that CXCL12 production by malignant epithelial cells precedes tumorigenesis and we confirm in a large cohort of patients with advanced EOC that CXCL12 expression level in EOC is not a valuable prognostic factor in itself. ClinicalTrials.gov: NCT00052468
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