英度科普-原來腫瘤細胞這麼美！

20 ElectrifyingMicroscopy Images of Cancer Cells

20種腫瘤細胞的電鏡下圖像

Researcherswho study cancer at the cellular level are offering a peek into their world bysharing images caught under electron microscopes, all collected as part of theNational Cancer Institutes Cancer Close Up 2016 project. Examples shownhere are both beautifully artistic and scientifically informative.

在細胞水平研究腫瘤的科研人員，提供了可以一窺他們研究領域的機會。他們分享了在電子顯微鏡下捕捉到的圖像。所收集到的圖像作為國家腫瘤機構的腫瘤癒合2016項目中使用。在這裡展示的圖片既具有藝術的美感，亦具有科教性。

Acrossdifferent cancer types, and even within the same tumor, cancer cells exhibit awide variety of molecular structures and characteristics. This so-calledheterogeneity poses difficult challenges to researchers trying to find betterways of managing the disease. This sample of clinical triple-negative breastcancer is stained for bone morphogenetic protein-11 (red); the Golgi markerGM130 (green); glycosylated proteins (white); and nuclei (blue), illustratingprofound molecular heterogeneity. Widefield fluorescence microscopy was used toobtain the image.

不同的腫瘤類型，甚至在相同的腫瘤中，癌細胞表現了多種多樣的分子結構和特徵。這種所謂的異質性給科研人員尋找管理疾病的最佳途徑造成了不小的挑戰。對此臨床三陰性乳腺癌的樣品進行染色，骨形態發生蛋白-11（紅色）；高爾基體標記GM130（綠色）；糖基化蛋白（白色）；細胞核（藍色），此圖解說了深奧的分子異質性。圖像由寬域熒光顯微鏡獲得。

Thisimage shows a human epithelial cell (DNA in blue) with increased numbers ofcentrosomes (green) amid a sea of normal cells in interphase. Centrosomeamplification can lead to chromosomal instability and an abnormal number ofchromosomes. These features are hallmarks of cancer and therefore potentialtargets for new therapies.

這張圖展示了在大量正常的間期細胞之間，中心體（綠色）數量增加的人體表皮細胞（DNA為藍色）。中心體擴增會導致染色體不穩定及其數量反常。這些特徵既是腫瘤的印記，同樣也是新療法的目標蛋白。

Thisimage shows HeLa cervical cancer cells stained for the cytoskeletalproteins actin (red) and tubulin (green). Cancer cells spread inthe body with the help of mutated genes that drive changes in the cellscytoskeleton—the protein filaments and microtubules that control cell shape andcontribute to cell movement. Examining how cancer cells use cytoskeletalproteins to move through the body may lead to targeted therapies that reversethese protein signals. Nuclear DNA appears in blue.

這張圖展示了染色後的海拉宮頸癌細胞，其中細胞骨架肌動蛋白（紅色），微管蛋白（綠色）。突變基因能夠幫助癌細胞擴散至全身，同樣突變基因也能夠驅動細胞骨架的改變——蛋白纖維和微管控制著細胞形狀也促使細胞運動。測試癌細胞是如何利用細胞骨架蛋白運動至全身的，可能會產生逆轉這些蛋白信號的靶向治療。細胞核中DNA呈藍色。

Theimage shows cell culture of human breast cancer conditionally reprogrammedcells. Fluorescent red color represents major histocompatibility complex(MHC)-I, and nuclei are shown in blue.

這張圖片展示了特定條件下重新編譯過的人類乳腺癌細胞。紅色熒光部分代表主要組織相容性複合體（MHC）-1，細胞核為藍色。

Treatingcancer in the brain is particularly difficult because most drug molecules arenot small enough to penetrate the blood-brain barrier. Researchers wonderwhether nanoparticles can serve as a drug-delivery mechanism. This image showsnanoparticles (red) being taken up in the brain of a live rat model withglioblastoma (in green). Nuclear DNA is in blue; tumor-associated macrophagesare in white.

腦部腫瘤的治療是非常困難的，這是因為大多數藥物分子並不是足夠小到能夠透過血腦屏障。科研人員考慮，納米級粒子是否可以作為藥物輸送機制。這張圖為納米級粒子（紅色）正在進入患有惡性膠質瘤（綠色）的活體大鼠腦部。細胞核DNA為藍色，腫瘤相關的巨噬細胞為白色。

MicroRNAs(miRNAs) are small molecules critical to gene expression. Researchers arecreating artificial miRNAs capable of binding to, and silencing, genesassociated with cancer. Delivering such miRNAs to their target is anotherchallenge. This image shows self-assembled nanoparticles (in red) carryingmiRNAs to an aggressive breast tumor in a mouse model and sticking to the tumortarget with the help of an adhesive glue.

微RNAs (miRNAs)是種小分子，它是基因表達的關鍵。科研人員正在發明一種人造的miRNAs，它能夠與致癌基因相結合併使其沉默。將此類miRNAs輸送至作用靶點是另一項挑戰。這張圖展示了在小鼠模型中，自體組裝的納米級粒子（紅色）將miRNAs攜帶至具有侵略性的乳腺腫瘤處，並在粘合劑的幫助下與腫瘤靶點緊密結合。

Epifluorescencemicroscopy of microtentacles forming on the surface of a breast tumor cell in afree-floating microenvironment. Microtentacles may play a role in tumormetastasis by helping cancer cells attach to blood vessel walls in distantparts of the body. New therapies that inhibit microtentacles could help reducemetastasis. Because microtentacles respond rapidly to drug treatments, drugscould be quickly tested for individual patients to improve precision medicine.

在可自由活動的微環境中乳腺癌細胞表面上形成的微型觸手的熒光顯微檢查。微型觸手通過幫助癌細胞附著於身體遠端的血管壁，從而對腫瘤轉移起著重要作用。新的治療法能夠抑制微型觸手，從而減少轉移。由於微型觸手對於藥物治療響應迅速，所以可以對獨立病患進行快速藥物測試，以完善用藥的精確度。

Whencancer cells metastasize to the bone microenvironment from the primary site,they secrete factors that stimulate osteoclasts both to resorb mineralized bonematrix and release stored growth factors that further enhance the growth ofcancer cells. Knowing how cancer cells spread to bone and cause bonedestruction is important to finding successful treatment. This image shows alarge multinucleated osteoclast (red) resorbing bone matrix (orange) adjacentto cancer cells (blue).

當癌細胞從原位點轉移至骨微環境中，他們藏匿了刺激破骨細胞的因子，從而再吸收礦化的骨基質，並釋放貯藏的未來能夠使腫瘤細胞加速生長的生長因子。了解癌細胞是怎樣轉移至骨骼的，以及是怎樣造成骨質破壞的，對於找到有效的治療方法是非常重要的。這張圖展示了一個大的多核破骨細胞（紅色）再吸收與癌細胞（藍色）相鄰的骨基質（橘色）。

Shownhere is a pseudo-colored scanning electron micrograph of an oral squamouscancer cell (white) being attacked by two cytotoxic T cells (red), part of anatural immune response. Nanomedicine researchers are creating personalizedcancer vaccines by loading neoantigens identified from the patients tumor intonanoparticles. When presented with immune stimulants, this activates thepatients own immune system, leading to expansion of tumor-specific cytotoxic Tcells.

這裡展示的是被兩個細胞毒素T細胞（紅色）攻擊的口腔鱗狀癌細胞（白色）的假色掃描電子顯微圖像，其中，細胞毒素T細胞是自身免疫應答的一部分。納米藥物科研人員正在研究一種將從患者腫瘤組織中識別的腫瘤抗原載入至納米級粒子中的個體化癌症疫苗。當與免疫激動劑同時出現時，它能夠激活患者自身的免疫系統，導致腫瘤特異性細胞毒性T細胞的增殖。

Thisimage of a breast cancer tumor and its microenvironment was obtained from alive mouse model using multiphoton microscopy and endogenous fluorescence. Thatis, the image was obtained without any fluorophores, stains, or dyes, usingonly the metabolic co-factors of NADH and FAD, which are already inside ofcells, along with second harmonic generation to see collagen. This techniquehas important clinical potential for patients who require label-free imaging,and may lead to more effective diagnoses and treatments. Tumor cells display incyan, macrophages in red, collagen fibers in green.

這張圖為乳腺癌腫瘤和它的微環境，是利用多光子顯微技術和內源性熒光從活的小鼠模型中獲得的。如此，該圖像的獲得沒有使用任何的熒光素、染色劑、或染料，只利用代謝協同因子NADH和FAD，以及二次諧波發生，以觀察膠原質。其中，代謝協同因子已NADH和FAD存在於細胞中。這項技術對於需要無標記圖像的患者具有重要的臨床潛力，並且會指導更加有效的診斷和治療。腫瘤細胞為藍綠色，巨噬細胞為紅色，膠原纖維為綠色。

Infectionwith certain types of human papillomavirus (HPV) is associated with variouscancers. Researchers are working to understand the processes by which HPV cantransform a healthy cell into a cancerous one. This image shows actin (stainedin green), a protein involved in cell motion, in HPV-16 E6- and E7-expressinghuman foreskin keratinocytes.

某種特定類型的人類乳頭瘤病毒（HPV）的感染與多種癌症相關。科研人員致力於了解HPV將健康細胞轉變為癌細胞的過程。這張圖片展示了肌動蛋白（染成綠色），細胞運動中涉及到的蛋白質，表達HPV-16 E6-和E7-的人類包皮角質細胞。

Ahigh level of the critical gene Sox10 is tied toaggressive breast cancer. In parts of the adult mammary gland, Sox10 is expressed in cells withhigher levels of stem cell activity and not in mature cells that lackdetectable stem cell activity. Progesterone receptor (red) indicatesnon-stem-like mammary cells, which show an inverse correlation with cellsexpressing Sox10 (blue). A protein calledcytokeratin-8 (green) shows the development of the gland.

高水平的關鍵基因Sox10與侵略性乳腺癌有關。在成人乳腺中，Sox10表達於幹細胞活性水平較高的細胞中，但不在檢測不到幹細胞活性的成熟細胞中表達。黃體酮受體（紅色）代表了非幹細胞樣的乳腺細胞，它與表達Sox10（藍色）的細胞呈負相關。細胞角蛋白-8（綠色）表現了腺體的發展。

Inthis image from a genetically engineered mouse model, lung cancer driven by theKRAS oncogene shows up in purple.As a key driver in many types of cancer, the KRAS gene makes apromising target for new cancer therapies.

這張圖來自於經基因工程處理過的小鼠模型，KRAS致癌基因驅動的肺癌表現為紫色。作為許多癌症類型的關鍵驅動器，KRAS基因是新的癌症療法中成功率更高的作用靶點。

Asshown here, lung cancer is associated with a vast stromal desmoplastic reaction(the "neighborhood") in which the connective tissue, associated withthe tumor, thickens similarly to scars. Cancer is in red; cell nuclei in cyan;stroma/desmoplasia in green; and an active stroma-specific marker in purple.

像在這裡展示的，肺癌與結締組織中大量的基質促結締組織增生反應（鄰近點）有關。與腫瘤相關的結締組織變厚，類似於疤痕。腫瘤是紅色，細胞核為藍綠色，基質/結締組織增生為綠色，活躍的基質特異性標記物為紫色。

Organoidsare miniature versions of organs grown in the lab. Organoid culture systemsoffer a powerful platform for the development of targeted therapies andprecision medicine by letting scientists easily create genetic or environmentalchanges (difficult or impossible in animal models or human patients) toidentify networks of genes that control cellular behaviors that give way totumors. This image shows an organoid that was grown from a single mammary stemcell. Researchers used this system to demonstrate how a single critical gene,called Sox10 (in blue), controls whethercells turn into dangerous mini "factories," rapidly churning out morecopies and variants of themselves. The Sox10 gene allowscells to migrate and to take on characteristics of other cells (plasticity). Incancer cells, these features lead to metastasis and drug resistance. Innerkeratin-8+ luminal cells (in green) are surrounded by peripheral keratin-14+basal cells (in red).

類器官是實驗室中器官生長的微管表現。類器官培養系統提供了一個有力的平台以發展靶向療法和精準用藥，通過讓科學家易於創造基因或環境上的變化（在動物模型或人類患者中無法獲得或很難獲得）來識別基因網路，該基因控制著為腫瘤生成讓步的細胞行為。該圖像展示了由單一乳腺幹細胞生成的類器官。科研人員利用這個系統來演示一個單一的關鍵基因，被稱作Sox10（藍色），是怎樣控制細胞是否會轉變成危險的小型「工廠」的，並迅速產生大量他們自己的複製體和變異體。Sox10允許細胞遷移，也呈現出其他細胞的特點（可塑性）。在腫瘤細胞中，這些特徵導致了轉移和藥物抵抗。內部角蛋白-8+腔細胞（綠色）被外部角蛋白-14+基底細胞（紅色）。

Humantumors often include slowly proliferating cancer cells that resist treatment.This image shows a cluster of slow-cycling (AKT-low/Hes1-high) breast cancercells (red) within a human ER+ primary breast tumor (cell nuclei in blue;rapidly cycling, AKT-high, cancer cells in green). Cancer cells enter anAKT-low state in response to decreased interaction of cell surface beta-1integrin with the extracellular matrix. AKT-low cancer cells within invasivebreast cancer tumors persist after combination chemotherapy and contribute totumor progression.

人類腫瘤通常包括對治療抵抗的緩慢增生的癌細胞。這張圖展示了人類ER+原發性乳腺癌（細胞核為藍色，快速循環，AKT-高，癌細胞為綠色）中一組緩慢循環（AKT-低/Hes1-高）乳腺癌細胞（紅色）。對降低細胞表面beta-1整合蛋白與細胞外基質內在聯繫的響應是，癌細胞進入到AKT-低態。在侵略性乳腺癌腫瘤中的AKT-低癌細胞會在聯合化療之後存活，並促進腫瘤發展。

Thisimage shows pancreatic cancer cells (nuclei in blue) growing as a sphereencased in membranes (red). By growing cancer cells in the lab, researchers canstudy factors that promote and prevent the formation of deadly tumors.

這張圖展示了胰腺癌細胞（細胞核為藍色）成長為一個球形，被細胞膜（紅色）包裹。通過在實驗室內培養癌細胞，科研人員可以研究能夠促進或阻止致命性腫瘤形成的因子。

Thisimage shows a triple-negative breast cancer cell undergoing retraction andapoptosis (cell death) after treatment with a combination of the chemotherapydrug cisplatin and a mitochondrial division inhibitor drug called mdivi-1.Actin in red; mitochondria in green; nuclei in blue. Understanding how drugswork at the molecular level contributes to better cancer treatments.

這張圖為化療藥物順鉑和線粒體分裂抑製劑mdivi-1聯合治療後三陰性乳腺癌細胞正在回縮和消亡（細胞死亡）。肌動蛋白為紅色，線粒體為綠色，細胞核為藍色。從分子水平了解藥物是如何起作用的有助於癌症更好的治療。

Vistais a molecule that regulates T lymphocytes and plays an important role inimmunity. Understanding more about Vistas functional role could helpresearchers develop immunotherapy approaches to the management of human cancer.This image shows a section of placenta tissue, specifically the cells that linevilli of placenta. The yellow color represents the presence of Vista protein;red represents the presence of CD8 protein; blue represents the cell nucleus.This assay shows that the Vista molecule is positively present in cells of theplacenta, indicating that placenta can be used as control tissue forimmunofluorescent staining assay of Vista in cancer research studies.

Vista是一種控制T淋巴細胞的分子，也對免疫起著非常重要的作用。詳細了解Vista的功能可以幫助科研人員發展免疫療法途徑來管理人類癌症。該圖片展示了胎盤組織的一部分，特別是胎盤絨毛細胞。黃色代表Vista蛋白質，紅色代表CD8蛋白質，藍色代表細胞核。該項試驗說明了Vista分子積極地出現在胎盤細胞中，也表明了在癌症研究中胎盤可以作為Vista熒光免疫染色試驗中的對照組織。

In this image from a mouse model of ovarian cancer,optically cleared tumor excised from a murine SKOV tumor seeded with CD63+cells reveals a high-resolution landscape of the three-dimensionaltumor-stromal interfaces that comprise the tumor microenvironment (TME). Secondharmonic signal (blue) and autofluorescent/GFP signals (green) demonstrates theinterplay of collagen II fibrils and vessels generated from angiogenesis. Theuse of optical tissue clearing has the potential to greatly improveresearchers ability to assess the anatomic, structural, and cellularconstituents that govern metastatic colonization in the TME at a single-cellresolution.

這張圖片來自於卵巢癌的小鼠模型中，可以清晰的看到，該腫瘤是從小鼠SKOV腫瘤上分離並利用CD63+細胞進行繁殖，它展示出了高清晰度的三維立體的腫瘤基質界面，其界面包含了腫瘤微環境（TME）。二次諧波信號（藍色）和自發熒光/GFP信號（綠色）展示了膠原II原纖維和由血管再生形成的血管之間的相互影響。光學組織清除能夠極大程度上提高科研人員評估解剖學、結構學、及細胞成分的能力。其中，細胞成分控制著單細胞水平下TME內的轉移性繁殖。

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