倫斯勒理工學(xué)院生物學(xué)家Lee Ligon已經(jīng)找到了在乳腺癌腫瘤細(xì)胞和周圍健康組織之間粘附連接中發(fā)揮重要的分子蛋白——鈣粘蛋白-23,。研究結(jié)果對認(rèn)識乳腺癌轉(zhuǎn)移早期階段非常有幫助,。
該研究結(jié)果發(fā)表在PLoS One雜志上,。研究由Ligon與倫斯勒博士生Maria Apostolopoulou共同完成。這項(xiàng)研究由美國癌癥協(xié)會資助,。
研究發(fā)現(xiàn)鈣粘蛋白-23存在于乳腺癌腫瘤組織內(nèi)和腫瘤周圍組織,，能幫助癌變腫瘤細(xì)胞與其鄰近的健康組織（基質(zhì)）相連接。
Ligon說：一旦癌細(xì)胞進(jìn)入基質(zhì),，腫瘤細(xì)胞侵襲性會大大提高,。癌組織的病理學(xué)研究已經(jīng)關(guān)注了腫瘤細(xì)胞會與基質(zhì)細(xì)胞之間的連接，但這些研究人員認(rèn)為這種連接是不重要,。
Ligon和她的團(tuán)隊(duì)試圖發(fā)現(xiàn)是什么分子參與了腫瘤細(xì)胞附著到周圍組織的過程,，以確定那些腫瘤細(xì)胞與周圍組織最初相接觸的點(diǎn)在癌癥發(fā)展中發(fā)揮作用。
在人乳腺癌中,，腫瘤常起源于上皮組織,。這些組織是由一個稱為上皮細(xì)胞的類型細(xì)胞組成。上皮細(xì)胞系存在于人體器官的內(nèi)部和許多功能結(jié)構(gòu)中,。在乳房組織中,，上皮細(xì)胞存在于乳管內(nèi)。當(dāng)上皮細(xì)胞開始分裂失控時,，它們最終打破乳管管道、侵入周圍組織或基質(zhì),?；|(zhì)由成纖維細(xì)胞和細(xì)胞外成分如膠原纖維等組成。在許多情況下,，侵襲性的癌變上皮細(xì)胞會到將附近基質(zhì)中成纖維細(xì)胞據(jù)為己有,，為自己所用。
Ligon和Apostolopoulou想了解上皮細(xì)胞是如何將自己粘附到成纖維細(xì)胞上的,。鈣粘蛋白分子家族在機(jī)體細(xì)胞之間粘附連接在一起的過程中發(fā)揮主要作用,。人類基因組中有80多個不同的cadherin家族成員。在大多數(shù)情況下,，鈣粘蛋白將兩個相同類型的細(xì)胞連接在一起,。對于乳腺癌腫瘤細(xì)胞和成纖維細(xì)胞來說，兩種截然不同的細(xì)胞也會粘在一起,。Ligon試圖確定是哪一個鈣粘素參與了腫瘤細(xì)胞和成纖維細(xì)胞之間的異型粘附,。Ligon等驚驚奇地發(fā)現(xiàn)鈣粘蛋白-23在上皮型腫瘤細(xì)胞與成纖維細(xì)胞之間的粘附也發(fā)揮關(guān)鍵作用。
Ligon說：以前研究未發(fā)現(xiàn)鈣粘蛋白23與癌癥有關(guān)。事實(shí)上,，以前研究只發(fā)現(xiàn)鈣粘蛋白23于耳朵和視網(wǎng)膜復(fù)雜的內(nèi)部運(yùn)作中發(fā)揮作用,。
我們對于一旦細(xì)胞連接后，產(chǎn)生的后續(xù)效應(yīng)仍然是未知的,。但據(jù)Ligon說：在癌組織中高水平的鈣粘蛋白23可能在腫瘤轉(zhuǎn)移的早期階段發(fā)揮關(guān)鍵性作用,。她說鈣粘蛋白23在癌癥的發(fā)展過程中是一個新的、潛在的非常重要的物質(zhì),，科學(xué)家們有必要對其開展進(jìn)一步研究,。（生物谷：Bioon）
doi:10.1371/journal.pone.0033289
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Cadherin-23 Mediates Heterotypic Cell-Cell Adhesion between Breast Cancer Epithelial Cells and Fibroblasts.
Maria Apostolopoulou, Lee Ligon
In the early stages of breast cancer metastasis, epithelial cells penetrate the basement membrane and invade the surrounding stroma, where they encounter fibroblasts. Paracrine signaling between fibroblasts and epithelial tumor cells contributes to the metastatic cascade, but little is known about the role of adhesive contacts between these two cell types in metastasis. Here we show that MCF-7 breast cancer epithelial cells and normal breast fibroblasts form heterotypic adhesions when grown together in co-culture, as evidenced by adhesion assays. PCR and immunoblotting show that both cell types express multiple members of the cadherin superfamily, including the atypical cadherin, cadherin-23, when grown in isolation and in co-culture. Immunocytochemistry experiments show that cadherin-23 localizes to homotypic adhesions between MCF-7 cells and also to heterotypic adhesions between the epithelial cells and fibroblasts, and antibody inhibition and RNAi experiments show that cadherin-23 plays a role in mediating these adhesive interactions. Finally, we show that cadherin-23 is upregulated in breast cancer tissue samples, and we hypothesize that heterotypic adhesions mediated by this atypical cadherin may play a role in the early stages of metastasis.
