Tumors are notoriously hard to kill. Attack them with chemotherapy, and they develop drug resistance; surgically remove them, and they may have already metastasized to other parts of the body. Now scientists have found that tumors have yet another trick up their sleeve: They can create their own blood supply by morphing into blood vessels. The observations, reported by two separate teams online today in Nature, could explain why drugs designed to choke off blood to brain tumors often fail.

        腫瘤向來以難以清除而臭名昭著,?；熾m可破壞，它們卻可以生發(fā)出抗藥性,；手術(shù)雖可切除,， 它們卻可能已經(jīng)轉(zhuǎn)移到身體的其他部位了。近期,，科學(xué)家們發(fā)現(xiàn)腫瘤的另一個詭計：它們可以形成血管來為自己供血,。這一由兩個不同的團隊提出的發(fā)現(xiàn)今天被《自然》雜志在線報道，這也許可以解釋為什么試圖切斷腦部腫瘤血液供應(yīng)的藥物并不起作用,。

The researchers drew the link between tumor cells and blood vessel cells with a series of experiments on glioblastomas—fast-growing brain tumors that contain tufts of thin, abnormal blood vessels. Neurosurgeon and stem cell scientist Viviane Tabar and colleagues at Memorial Sloan-Kettering Cancer Center in New York City first took glioma samples from the operating room and looked for chromosomal abnormalities in the endothelial cells lining the tumor's blood vessels. They found patterns exactly like those in cells from the tumor itself, suggesting that at least some of the blood vessel cells came from the tumor.

        研究者們通過在膠質(zhì)母細胞瘤上的一系列實驗歸納出了腫瘤細胞和血管細胞的聯(lián)系,。其中，膠質(zhì)母細胞瘤是一種生長很快的腦部腫瘤,，伴隨有簇生的薄而異常的血管,。作為神經(jīng)外科醫(yī)生，同時是干細胞研究專家的維維恩 塔巴和其在紐約的斯隆-凱特琳癌癥中心的同事最先從手術(shù)室中獲取神經(jīng)膠質(zhì)瘤樣本,，并且檢視了腫瘤血管邊沿的內(nèi)皮細胞的染色體異常情況,。他們發(fā)現(xiàn)，那些染色體的形態(tài)和腫瘤自身細胞的完全相同,，說明至少一些血管細胞是來自腫瘤內(nèi)部的,。

The researchers then sorted glioma cells into different types using antibodies that stick to specific proteins on a cell's surface. They showed that the cells that give rise to blood vessels are an immature cancer cell, known as a stemlike cancer cell. Finally, the researchers injected these cancer stem cells into the brains of mice with weakened immune systems and then examined the blood vessels within the resulting tumors. The vessels stained positive for antibodies to human endothelial cells, again showing that some of the cells had to come from the tumor.

        研究者們接下來通過特異性結(jié)合細胞表面蛋白質(zhì)的抗體將神經(jīng)膠質(zhì)瘤細胞分成不同的類型。他們證明形成了血管的細胞是不成熟的癌細胞,，常被稱為干細胞樣癌細胞,。最后，研究者們將這些癌癥干細胞注射到免疫低下的小鼠腦部并檢測生成的腫瘤中的血管,。這些血管對人類內(nèi)皮細胞抗體呈陽性,，再一次證明了一些血管細胞來自腫瘤自身。

The bottom line: "There is plasticity within the tumor, and it can make its own blood vessels," says Tabar. She says that this could explain why cancer drugs aimed at choking off a tumor's blood supply by blocking growth signals, known as angiogenesis inhibitors, usually stop working within about 6 months. When her team added one of the antiangiogenesis drugs to a culture of the cancer cells, the drug stopped immature blood vessel cells from maturing but didn't block the stem cells from developing into the immature blood vessel cells. Because tumor cells are genetically unstable, they may easily find ways to bypass the antiangiogenesis drugs, Tabar says.

        塔巴表示,，研究證明腫瘤內(nèi)部具有可塑性,，它可以形成自己的血管。她說這也就可以解釋為什么試圖通過血管生成抑制因子來阻斷血管生長信號而阻斷腫瘤血液供應(yīng)的藥物通常在六周內(nèi)失去作用,。當(dāng)她的團隊將一種抗血管生成的藥物加入到培養(yǎng)的癌細胞中時,，藥物可以終止不成熟的血管細胞的成熟過程，但卻不能阻止干細胞發(fā)展成為不成熟的血管細胞,。塔巴表示,，由于腫瘤細胞在遺傳上的不穩(wěn)定性，它們可以輕易躲過抗血管生成藥物的攻擊,。

A separate team led by Ruggero De Maria at the Istituto Superiore di Sanità in Rome published a similar set of experiments today. Both teams suggest that combining antiangiogenesis drugs with another drug that stops the stem cells from maturing might be a way to overcome resistance in gliomas and perhaps other cancers.

        另一個位于羅馬的國家衛(wèi)生研究所的研究組也發(fā)表了一套類似的實驗,。兩個研究組都提到，通過結(jié)合使用抗腫瘤生成藥物和另一種可以阻斷干細胞成熟的藥物也許可以解決神經(jīng)膠質(zhì)瘤以及其他癌癥出現(xiàn)的抗性的問題,。

Other papers have hinted that cancer cells might give rise to blood vessel cells, but the two studies reporting essentially the same result confirm that suspicion, says angiogenesis researcher David Cheresh of the University of California, San Diego. "These two papers will put the controversy to rest."

        其他的文章曾經(jīng)暗示,，癌癥干細胞有可能生發(fā)出血管細胞,，這兩份研究的報告證實了這個假設(shè)。加州大學(xué)圣迭戈分校研究血管生成的大衛(wèi) 查萊仕指出,，這兩份報告將會停息這些爭論了,。