Höckel Michael, Behn Ulrich
Department of Gynecology, Women's and Children's Center, University of Leipzig, Leipzig, Germany.
Leipzig School of Radical Pelvic Surgery, University of Leipzig, Leipzig, Germany.
Front Oncol. 2019 May 29;9:416. doi: 10.3389/fonc.2019.00416. eCollection 2019.
Local spread patterns of malignant tumors follow permissive tissue territories, i.e., cancer fields, as shown for cervical and vulvar carcinoma. The cancer fields are associated in reverse order to the mature derivatives of the morphogenetic fields instrumental in the stepwise development of the tissue from which the tumor arose. This suggests that cancer progression may be linked to morphogenesis by inversion of the cellular bauplan sequence. Successive attractor transitions caused by proliferation-associated constraints of topobiological information processing are proposed for both morphogenesis and cancer. In morphogenesis these transitions sequentially activate bauplans with increasing complexity at decreasing plasticity restricting the permissive territories of the progenitor cell populations. Somatic mutations leading to cell proliferation in domains normally reserved for differentiation trigger the inverse cascade of bauplan changes that increase topobiological plasticity at decreased complexity and stepwise enlarge the permissive territory of neoplastic cells consistent with the clinical manifestations of cancer. The order provided by the sequence of attractor transitions and the defined topography of the permissive territories can be exploited for more accurate tumor staging and for locoregional tumor treatment either by surgery or radiotherapy with higher curative potential.
恶性肿瘤的局部扩散模式遵循允许性组织区域，即癌场，如宫颈癌和外阴癌所示。癌场与形态发生场的成熟衍生物呈相反顺序相关，这些形态发生场在肿瘤起源组织的逐步发育中起作用。这表明癌症进展可能通过细胞bauplan序列的反转与形态发生相关联。对于形态发生和癌症，都提出了由拓扑生物学信息处理的增殖相关约束引起的连续吸引子转变。在形态发生过程中，这些转变依次激活bauplans，随着可塑性降低，复杂性增加，从而限制祖细胞群体的允许区域。导致细胞在通常用于分化的区域增殖的体细胞突变触发bauplan变化的反向级联反应，这种反应在复杂性降低的情况下增加拓扑生物学可塑性，并逐步扩大肿瘤细胞的允许区域，这与癌症的临床表现一致。吸引子转变序列提供的顺序以及允许区域的明确地形可用于更准确的肿瘤分期以及通过具有更高治愈潜力的手术或放射疗法进行局部区域肿瘤治疗。
