Tu Shi-Ming, Moran Cesar, Norton William, Zacharias Niki M
Division of Hematology and Oncology, University of Arkansas for Medical Sciences.
Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center.
Semin Diagn Pathol. 2023 Jan;40(1):63-68. doi: 10.1053/j.semdp.2022.06.012. Epub 2022 Jun 15.
Metastasis may be the secret weapon cancer uses to dominate and subjugate, to persist and prevail. However, it is no longer a secret when we realize that a stem cell has the same ways and means to fulfill its own omnipotence and accomplish its own omnipresence… and when we realize that a cancer cell has its own version of stem-ness origin and stem-like nature. In this perspective, we discuss whether stem-ness enables metastasis or mutations drive metastasis. We ponder about low-grade versus high-grade tumors and about primary versus metastatic tumors. We wonder about stochasticity and hierarchy in the genesis and evolution of cancer and of metastasis. We postulate that metastasis may hold the elusive code that makes or breaks a stem-cell versus a genetic theory of cancer. We speculate that the vaunted model of multistep carcinogenesis may be in error and needs some belated remodeling and a major overhaul. We propose that subsequent malignant neoplasms from germ cell tumors and donor-derived malignancies in organ transplants are quintessential experiments of nature and by man that may eventually empower us to elucidate a stem-cell origin of cancer and metastasis. Unfortunately, even the best experiments of cancer and of metastasis will be left unfinished, overlooked, or forgotten, when we do not formulate a proper cancer theory derived from pertinent and illuminating clinical observations. Ultimately, there should be no consternations when we realize that metastasis has a stem-cell rather than a genetic origin, and no reservations when we recognize that metastasis has been providing us some of the most enduring tests and endearing proofs to demonstrate that cancer is indeed a stem-cell rather than a genetic disease after all.
转移可能是癌症用来主宰、征服、持续存在并占据上风的秘密武器。然而，当我们意识到干细胞拥有实现自身全能性并达成自身无所不在的相同方式和手段时……当我们意识到癌细胞具有自身版本的干性起源和类干细胞性质时，转移就不再是秘密了。从这个角度出发，我们探讨是干性促成了转移还是突变驱动了转移。我们思考低级别肿瘤与高级别肿瘤以及原发性肿瘤与转移性肿瘤的问题。我们对癌症及转移发生与演变过程中的随机性和层级性感到好奇。我们推测转移可能掌握着决定癌症干细胞理论与基因理论成败的 elusive 密码。我们猜测备受推崇的多步骤致癌模型可能有误，需要进行一些迟来的重塑和重大修正。我们提出，生殖细胞肿瘤引发的后续恶性肿瘤以及器官移植中供体来源的恶性肿瘤是自然界和人类进行的典型实验，最终可能使我们得以阐明癌症及转移的干细胞起源。不幸的是，当我们没有从相关且具有启发性的临床观察中推导出恰当的癌症理论时，即使是关于癌症和转移的最佳实验也会被搁置、忽视或遗忘。最终，当我们认识到转移起源于干细胞而非基因时，不应感到惊愕；当我们认识到转移一直在为我们提供一些最持久的检验和最有力的证据，以证明癌症实际上毕竟是一种干细胞疾病而非基因疾病时，也不应有所保留。 （注：原文中“elusive”未准确翻译，可能是作者生造的词，这里按字面意思保留，实际含义需结合上下文确定）
