Drosophila mxc^mbn1 mutant exhibits severe hyperplasia in larval hematopoietic tissue called the lymph glands (LGs). However, the malignant nature of these cells remains unknown. We aimed to identify if mxc^mbn1 LG cells behave as malignant tumor cells and uncover the mechanism(s) underlying the malignancy of the mutant hemocytes. When mutant LG cells were allografted into normal adult abdomens, they continued to proliferate; however, normal LG cells did not proliferate. Mutant circulating hemocytes also attached to the larval central nervous system (CNS), where the basement membrane was disrupted. The mutant hemocytes displayed higher expression of matrix metalloproteinase (MMP) 1 and MMP2 and higher activation of the c-Jun N-terminal kinase (JNK) pathway than normal hemocytes. Depletion of MMPs or JNK mRNAs in LGs resulted in reduced numbers of hemocytes attached to the CNS, suggesting that the invasive phenotype involved elevated expression of MMPs via hyperactivation of the JNK pathway. Moreover, hemocytes with elongated filopodia and extra lamellipodia were frequently observed in the mutant hemolymph, which also depended on JNK signaling. Thus, the MMP upregulation and overextension of actin-based cell protrusions were also involved in hemocyte invasion in mxc^mbn1 larvae. These findings contribute to the understanding of molecular mechanisms underlying mammalian leukemic invasion.

中文翻译：

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基质金属蛋白酶的异位表达和通过 JNK 激活的丝状伪足延伸参与果蝇 mxc 突变体的血液肿瘤细胞的侵袭

果蝇 mxc ^mbn1突变体在称为淋巴腺 (LG) 的幼虫造血组织中表现出严重增生。然而，这些细胞的恶性性质仍然未知。我们的目的是确定mxc ^mbn1 LG 细胞是否表现为恶性肿瘤细胞，并揭示突变血细胞恶性肿瘤的机制。当突变的 LG 细胞被同种异体移植到正常成人腹部时，它们会继续增殖；然而，正常的 LG 细胞并没有增殖。突变的循环血细胞还附着在幼虫中枢神经系统（CNS）上，该系统的基底膜被破坏。与正常血细胞相比，突变血细胞表现出更高的基质金属蛋白酶 (MMP) 1 和 MMP2 表达以及更高的 c-Jun N 末端激酶 (JNK) 通路激活。LG 中 MMP 或 JNK mRNA 的耗竭导致附着在 CNS 上的血细胞数量减少，表明侵袭表型涉及通过 JNK 通路过度激活而导致 MMP 表达升高。此外，在突变血淋巴中经常观察到具有拉长丝状伪足和额外片状伪足的血细胞，这也依赖于 JNK 信号传导。因此，MMP 的上调和基于肌动蛋白的细胞突起的过度延伸也参与了mxc ^mbn1幼虫的血细胞侵袭。这些发现有助于理解哺乳动物白血病侵袭的分子机制。