Feinberg School of Medicine and Kellogg School of Management, Northwestern University, Chicago, Illinois.
Cancer Res. 2022 May 16;82(10):1870-1871. doi: 10.1158/0008-5472.CAN-22-0819.
The invasive progression of cancer known as metastasis remains strongly associated with morbidity and lethality. New meaningful therapeutic interventions could be derived from a better understanding of the underlying processes driving cancer cell seeding and proliferation at secondary sites. Emerging findings regarding the heterogeneity of cancer cells observed in metastases have led us to revisit concepts surrounding metastatic fitness. Novel model systems to study the markers of cancer stem cell plasticity and their evolution during metastatic growth have uncovered that dynamic and heterogeneous cancer cell populations are observed during metastatic disease progression. Heinz and colleagues studied the heterogeneity of colorectal carcinomas, where primary tumors evolve alongside an epithelium well characterized for its self-renewing stem cell population. Their work revealed a functional dynamic interplay in the organization of the metastatic lesions as they transition from stagnating to expanding nodules, wherein the heterogeneous mixture of cancer cell stem cells with more differentiated cancer cells is essential for metastatic outgrowth. Their work supports that dynamic YAP signaling enables the growth-permissive heterogeneous composition of the metastatic nodule, in contrast with growth-restricted homogeneous compositions. See related article by Heinz et al., p. 1953.
癌症的侵袭性进展，即转移，仍然与发病率和死亡率密切相关。如果能更好地了解驱动癌细胞在次级部位播种和增殖的潜在过程，就可能产生新的有意义的治疗干预措施。转移中观察到的癌细胞异质性的新发现，促使我们重新审视与转移性适应性相关的概念。研究癌症干细胞可塑性标志物及其在转移生长过程中进化的新型模型系统，揭示了在转移性疾病进展过程中观察到动态和异质的癌细胞群体。Heinz 及其同事研究了结直肠癌的异质性，其中原发性肿瘤与具有自我更新干细胞群体的上皮细胞一起进化。他们的工作揭示了转移性病变组织从停滞到扩展结节的转变过程中存在功能动态相互作用，其中具有更多分化癌细胞的癌细胞干细胞的异质混合物对于转移生长至关重要。他们的工作表明，动态 YAP 信号有助于转移结节的生长许可性异质组成，而不是生长受限的同质组成。参见 Heinz 等人的相关文章，第 1953 页。
