普遍認為，只有基底樣細胞具有干細胞特性,，可以形成侵入性腫瘤,。但是，PNAS上一篇新研究提出了另一觀點,，它指出,，導管樣細胞是一種癌細胞亞群，無可檢測的干細胞特性,，具致瘤性,、高侵襲性，能產生更巨大的腫瘤,。這對于乳腺癌診斷與治療可能具有重要意義,，將來的個性化癌癥醫(yī)學也如此。
當前流行的觀點是：如果癌癥干細胞被殺死,，乳腺癌就是一種可治療的疾病,。但是，亞型致瘤細胞的存在則告訴我們,，腫瘤需要徹底根除,，不只是基底樣細胞。
許多乳腺癌開始于乳導管和小葉,，它們由基底樣細胞包圍的導管樣細胞組成,，這兩種細胞是最常見的兩種人類乳腺癌細胞，因它們與正常乳腺2個主要譜系相似性而命名為導管樣和基底樣,。在過去的幾年里,，廣泛認為基底樣細胞無干細胞的未分化特性，是侵入性腫瘤的起源,。然而,，大多數乳腺癌表現(xiàn)出管腔細胞分化，于是研究人員研究了基底樣細胞譜系內導管樣分化的細胞是否可能成為致瘤細胞,，或者這些導管樣細胞必須獲得基底樣特質才變成惡性細胞,。
研究發(fā)現(xiàn)，導管樣細胞沒有特異的基底細胞樣特性,，在實驗測試小鼠上完全能引發(fā)腫瘤,，導管樣細胞產生的腫瘤實際上遠遠大于基底樣細胞產生的。另外，在侵入性測試中,，這些純導管樣細胞表型的侵襲性強于基底樣細胞,。這表明，基底樣細胞象當前界定的那樣,，不是乳腺腫瘤侵襲性的必要條件,，單一腫瘤內存在多種具致瘤潛能的細胞。這對當前致瘤性層次喪失或分化喪失的假設提出了質疑,。
研究中用乳粘蛋白（MM,，milk mucin）作為分離導管樣癌細胞的標志，其中乳粘蛋白是一種聚糖,，這種糖分子廣泛存在于細胞表面和細胞信號通路核心,，用M18抗體檢測。CD271蛋白為基底樣細胞的標志,，用ME20.4抗體檢測,。
此外，導管樣乳腺癌細胞形成強侵入性腫瘤的能力決定于糖蛋白基因GCNT1的表達,，這個基因是用M18抗體檢測MM聚糖所必需的,；如果侵襲性導管樣癌細胞表達MM抗原決定簇，抑制GCNT1活性就能阻止它們的侵襲行為,。因而,，可推測這一發(fā)現(xiàn)可能具有潛在的臨床重要性，對將來的個性化醫(yī)學也可能有重要意義,。（生物谷bioon.com）
doi:10.1073/pnas.1203203109
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Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity
Jiyoung Kim, René Villadsen, Therese Sørlie, Louise Fogh,Signe Z. Grønlund, Agla J. Fridriksdottir, Irene Kuhn, Fritz Rank,Vera Timmermans Wielenga, Hiroko Solvang, Paul A. W. Edwards,Anne-Lise Børresen-Dale, Lone Rønnov-Jessen, Mina J. Bissell, and Ole William Petersen
The majority of human breast cancers exhibit luminal epithelial differentiation. However, most aggressive behavior, including invasion and purported cancer stem cell activity, are considered characteristics of basal-like cells. We asked the following questions: Must luminal-like breast cancer cells become basal-like to initiate tumors or to invade? Could luminally differentiated cells within a basally initiated hierarchy also be tumorigenic? To answer these questions, we used rare and mutually exclusive lineage markers to isolate subsets of luminal-like and basal-like cells from human breast tumors. We enriched for populations with or without prominent basal-like traits from individual tumors or single cell cloning from cell lines and recovered cells with a luminal-like phenotype. Tumor cells with basal-like traits mimicked phenotypic and functional behavior associated with stem cells assessed by gene expression, mammosphere formation and lineage markers. Luminal-like cells without basal-like traits, surprisingly, were fully capable of initiating invasive tumors in NOD SCID gamma (NSG) mice. In fact, these phenotypically pure luminal-like cells generated larger and more invasive tumors than their basal-like counterparts. The tumorigenicity and invasive potential of the luminal-like cancer cells relied strongly on the expression of the gene GCNT1, which encodes a key glycosyltransferase controlling O-glycan branching. These findings demonstrate that basal-like cells, as defined currently, are not a requirement for breast tumor aggressiveness, and that within a single tumor there are multiple "stem-like" cells with tumorigenic potential casting some doubt on the hypothesis of hierarchical or differentiative loss of tumorigenicity.
