Hardy C L, Balducci L
J Natl Cancer Inst. 1986 Mar;76(3):535-40.
Lewis lung carcinoma (LLC) of C57BL/6 mice, a transplantable tumor widely metastatic by 6-7 days post implant (PI), caused hematopoietic alterations such as progressive anemia (hemoglobin: day 1 PI, 11.0 g/dl; day 19 PI, 7.8 g/dl), neutrophilia (neutrophils: day 1 PI, 2 X 10(3)/microliter; day 19 PI, 22 X 10(3)/microliter), and marrow and splenic myeloid hyperplasia (marrow myeloid-to-erythroid ratio: day 1 PI, 1:1; day 7 PI, 3:1). Accompanying these changes were an increased concentration of marrow granulocyte-macrophage colony-forming units (culture) (GM-CFUC) (day 3 PI, LLC 185 +/- 27% of control; day 19 PI, LLC 265 +/- 10% of control) and accelerated cycling of these myeloid progenitors [day 3 PI, LLC 45.3 +/- 6.5% GM-CFUC in cycle vs. sham (media) injected 17.5 +/- 10.5%; day 7 PI, LLC 52.2 +/- 2.5% vs. sham (media) injected 29.8 +/- 9.8%; day 11 PI, LLC 56.2 +/- 4.4% vs. sham (media) injected 22.2 +/- 14%]. This study questioned whether enhanced hematopoiesis was a result of progressive tumor growth or whether the injection of tumor cells could evoke the response. By use of groups of C57BL/6 mice given an injection of live LLC cells, x-irradiated killed LLC cells, or media, the hematopoietic response to live LLC cells versus dead LLC cells could be dissected. A biphasic colony-stimulating activity (CSA) response in the sera of tumor bearers was found to account for the myelopoietic changes. The first wave of CSA from days 1 to 3 PI stimulated 168 +/- 3.7% more GM-CFUC than control sera and was likely released by dead cells of the tumor inoculum; the second wave from day 7 onward stimulated 220 +/- 7.6% more colonies and was a result of the enlarging tumor mass. Tumor growth was necessary for GM-CFUC proliferation, and the declining growth fraction at day 19 in LLC-bearing mice suggested that hematopoietic exhaustion was a consequence of tumor growth.
C57BL/6小鼠的Lewis肺癌（LLC）是一种可移植肿瘤，植入后6 - 7天广泛转移，会引起造血改变，如进行性贫血（血红蛋白：植入后第1天，11.0 g/dl；植入后第19天，7.8 g/dl）、中性粒细胞增多（中性粒细胞：植入后第1天，2×10³/微升；植入后第19天，22×10³/微升），以及骨髓和脾脏髓系增生（骨髓髓系与红系比例：植入后第1天，1:1；植入后第7天，3:1）。伴随这些变化的是骨髓粒细胞 - 巨噬细胞集落形成单位（培养）（GM - CFUC）浓度增加（植入后第3天，LLC为对照的185±27%；植入后第19天，LLC为对照的265±10%），以及这些髓系祖细胞的加速循环[植入后第3天，LLC处于周期中的GM - CFUC为45.3±6.5%，而假注射（培养基）组为17.5±10.5%；植入后第7天，LLC为52.2±2.5%，假注射（培养基）组为29.8±9.8%；植入后第11天，LLC为56.2±4.4%，假注射（培养基）组为22.2±14%]。本研究质疑造血增强是肿瘤逐渐生长的结果，还是肿瘤细胞注射可引发该反应。通过对注射活LLC细胞、经X射线照射杀死的LLC细胞或培养基的C57BL/6小鼠组进行研究，可剖析对活LLC细胞与死LLC细胞的造血反应。发现肿瘤携带者血清中的双相集落刺激活性（CSA）反应可解释髓系造血变化。植入后第1天至第3天的第一波CSA刺激的GM - CFUC比对照血清多168±3.7%，可能由肿瘤接种物的死细胞释放；第7天及以后的第二波刺激的集落多220±7.6%，是肿瘤块增大的结果。GM - CFUC增殖需要肿瘤生长，植入LLC小鼠第19天生长分数下降表明造血耗竭是肿瘤生长的后果。
