The bacterial lodgers in cancer cells may hinder or help treatment
癌細胞中的細菌寄宿者可能阻礙或協助治療
Cancer cells are comfy havens for bacteria. That conclusion arises from a rigorous study of over 1,000 tumor samples of different human cancers. The study, headed by researchers at the Weizmann Institute of Science, found bacteria living inside the cells of all the cancer types – from brain to bone to breast cancer – and even identified unique populations of bacteria residing in each type of cancer.
癌細胞是細菌的舒適天堂。那個結論來自1千多個，不同人類癌症腫瘤樣品的嚴密研究。該項由以色列魏茨曼科學研究所，研究人員們領導的研究發現了，生存於所有癌腫類型(從腦癌、骨癌到乳腺癌)之細胞內的細菌。甚至確認了，存在於每種癌腫中的獨特細菌種群。
The research suggests that understanding the relationship between a cancer cell and its “mini-microbiome” may help predict the potential effectiveness of certain treatments or may point, in the future, to ways of manipulating those bacteria to enhance the actions of anticancer treatments. The findings of this study were published in Science.
該項研究暗示，瞭解癌細胞與其“微型微生物體”之間的關係，可能有助於預測某些治療的潛在效果，或於未來可能朝向，操縱那些細菌，來增強抗癌治療的方法。該項研究的此些研究發現，發表於《科學》期刊。
Dr. Ravid Straussman of the Institute’s Molecular Cell Biology Department had, several years ago, discovered bacteria lurking within human pancreatic tumor cells; these bacteria were shown to protect cancer cells from chemotherapy drugs by “digesting” and inactivating these drugs. When other studies also found bacteria in tumor cells, Straussman and his team wondered whether such hosting might be the rule, rather than the exception.
若干年前，魏茨曼科學研究所分子細胞生物學系的Ravid Straussman博士發現了，潛伏於人類胰腺腫瘤細胞內的細菌。經證實，此些細菌藉由“吸收”及鈍化藥物，來保護癌細胞免於化療藥物。當諸多其他研究，在腫瘤細胞中，也發現細菌時。Straussman及其團隊極想知曉，這樣的寄宿是否是種常態，而不是例外。
To find out, Drs. Deborah Nejman and Ilana Livyatan in Straussman’s group and Dr. Garold Fuks of the Physics of Complex Systems Department worked together with a team of oncologists and researchers around the world. The work was also led by Dr. Noam Shental of the Mathematics and Computer Science Department of the Open University of Israel.
為了查明，Straussman團隊中的Deborah Nejman、Ilana Livyatan博士，及複雜系統系的物理學Garold Fuks博士，與一支世界各地的腫瘤學家及研究人員團隊一起進行了研究。該項研究也由，以色列開放大學數學暨計算機科學系的Noam Shental博士所領導。
Ultimately, the team would produce a detailed study describing, in high resolution, the bacteria living in these cancers – brain, bone, breast, lung, ovary, pancreas, colorectal and melanoma. They discovered that every single cancer type, from brain to bone, harbored bacteria and that different cancer types harbor different bacteria species.
最終，該團隊竟然以高解析方式作出了，描述生存於腦癌、骨癌、乳腺癌、肺癌、卵巢癌、胰腺癌、結腸直腸癌及黑色素瘤中的詳細研究。他們發現，從大腦到骨頭的每一種癌腫類型皆窩藏了細菌，且不同癌腫類型窩藏不同細菌種類。
It was the breast cancers, however, that had the largest number and diversity of bacteria. The team demonstrated that many more bacteria can be found in breast tumors compared to the normal breast tissue surrounding these tumors, and that some bacteria were preferentially found in the tumor tissue rather than in the normal tissue surrounding it.
不過，具有最多數量及多樣細菌的是乳腺癌。該團隊證實，相較於乳腺腫瘤周遭的正常乳腺組織，在此些腫瘤中，能發現更多細菌，且有些細菌是在此種腫瘤中，而不是其周遭正常組織中，優先被發現。
To arrive at these results, the team had to overcome several challenges. For one, the mass of bacteria in a tumor sample is relatively small, and the researchers had to find ways to focus on these tiny cells-within-cells.
為了達成上述研究結果，該團隊必須克服若干挑戰。舉個例說，於腫瘤樣本中，細菌的質量相當小，因此這些研究人員必需找到，聚焦於此些微小細胞內細胞的方法。
They also had to eliminate any possible outside contamination. To this end they used hundreds of negative controls and created a series of computational filters to remove the traces of any bacteria that could have come from outside the tumor samples.
他們也必須消除任何可能的外部污染。為此，他們使用了數百個陰性對照樣本，並創造了一系列計算過濾器，來移除可能已經來自腫瘤樣本外部的任何微量細菌。
The team was able to grow bacteria directly from human breast tumors, and their results proved that the bacteria found in these tumors are alive. Electron microscopy visualization of these bacteria demonstrated that they prefer to nestle up in a specific location inside the cancer cells – close to the cell nucleus.
該團隊能直接從人類乳腺腫瘤培養出細菌，因此他們的研究結果證實，在此些腫瘤中，發現的細菌是活著的。電子顯微鏡視覺化這些細菌，證實它們較喜歡處於癌細胞中，靠近細胞核的特定位置。
圖1. 該電子顯微鏡影像揭露了，生存於腫瘤細胞中的細菌。 (圖援用自原文)
The team also reported that bacteria can be found not only in cancer cells, but also in immune cells that reside inside tumors. “Some of these bacteria could be enhancing the anticancer immune response, while others could be suppressing it – a finding that may be especially relevant to understanding the effectiveness of certain immunotherapies,” says Straussman.
該團隊也提出了，細菌不僅能在癌細胞中發現，而且也於存在腫瘤內的免疫細胞中發現。Straussman宣稱：「其中一些細菌可能增強抗癌免疫反應，而其他細菌可能抑制此反應。這是一項，或許與瞭解某些免疫療法，特別有關的研究發現。」
Indeed, when the team compared the bacteria from groups of melanoma samples, they found that different bacteria were enriched in those melanoma tumors that responded to immunotherapy as compared to those that had a poor response.
實際上，當該團隊比較了，來自數組黑色素瘤樣本的細菌時。他們發現，當與那些反應不佳之黑色素腫瘤作比較時，在那些對免疫療法作出反應的黑色素腫瘤中，具有豐富的不同細菌。
Straussman thinks that the study can also begin to explain why some bacteria like cancer cells and why each cancer has its own typical microbiome: The differences apparently come down to the choice of amenities offered in each kind of tumor-cell environment.
Straussman認為，該項研究也能開始解釋，為何某些細菌喜歡癌細胞，及為什麼每一種癌腫皆有其自身的典型微生物體。此些差異顯然可歸結於，在每一種腫瘤細胞環境中，提供之舒適生存區的選擇。
That is, the bacteria may live off certain metabolites that are overproduced by or stored within the specific tumor types. For example, when the team compared the bacteria found in lung tumors from smokers with those from patients who had never smoked, they found variances.
也就是說，此些細菌可能寄食於，由特定腫瘤類型過度產生，或儲存的代謝產物。譬如，當該團隊比較，來自吸菸者與來自那些不曾吸菸者，肺腫瘤中的細菌時，他們發現了差異。
These differences stood out more clearly when the researchers compared the genes of these two groups of bacteria: Those from the smokers’ lung cancer cells had many more genes for metabolizing nicotine, toluene, phenol and other chemicals that are found in cigarette smoke.
當此些研究人員比較這兩群細菌的基因時，那些來自吸菸者肺癌細胞的細菌具有較多，代謝香菸煙霧中發現之尼古丁、甲苯、苯酚及其他化學物質的基因。
In addition to showing that some of the most common cancers shelter unique populations of bacteria within their cells, the researchers believe that the methods they have developed to identify signature microbiomes with each cancer type can now be used to answer some crucial questions about the roles these bacteria play:
除了證實，某些最常見之癌腫掩護其細胞內獨特的細菌種群。此些研究人員認為，他們已經開發來確認，每一癌腫類型之特徵微生物體的方法，目前能被用來回答，有關此些細菌扮演之角色的一些關鍵問題：
Are the bacteria freeloaders on the cancer cell’s surplus metabolites, or do they provide a service to the cell? At what stage do they take up residence? How do they promote or hinder the cancer’s growth? What are the effects that they have on response to a wide variety of anticancer treatments?
此些細菌是針對癌細胞之多餘代謝物的寄食者？或它們為此種細胞提供服務？它們在什麼階段開始駐留？它們如何促進或阻礙癌腫生長？什麼是它們對多種抗癌療法作出反應，具有的影響？
“Tumors are complex ecosystems that are known to contain, in addition to cancer cells, immune cells, stromal cells, blood vessels, nerves, and many more components, all part of what we refer to as the tumor microenvironment. Our studies, as well as studies by other labs, clearly demonstrate that bacteria are also an integral part of the tumor microenvironment. We hope that by finding out how exactly they fit into the general tumor ecology, we can figure out novel ways of treating cancer,” Straussman says.
Straussman宣稱：「腫瘤是已知除了癌細胞、免疫細胞、基質細胞、血管、神經及更多成分外，具有他們所稱為腫瘤微環境之所有部分的複雜生態體系。他們及其他實驗室進行的諸多研究明確證實，細菌也是腫瘤微環境構成所不可或缺的部分。他們期盼，藉由查明究竟它們確切如何適應這種普遍的腫瘤生態環境，能找出治療癌腫的新方法。」
原文網址：https://wis-wander.weizmann.ac.il/life-sciences/cells-inside-cells-bacteria-live-cancer-cells
翻譯：許東榮
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