Tarek Alshaimaa, El-Sayed Shrouk Khalaf, Woodward Wendy A, El-Shinawi Mohamed, Hirshon Jon Mark, Mohamed Mona Mostafa
Department of Zoology, Faculty of Science, Cairo University, Giza 12613, Egypt.
Maadi Military Hospital, Maadi, Cairo 11711, Egypt.
Curr Issues Mol Biol. 2022 Jun 17;44(6):2730-2744. doi: 10.3390/cimb44060187.
Inflammatory breast cancer (IBC) is an aggressive phenotype with a high recurrence and low survival rate. Approximately 90% of local breast cancer recurrences occur adjacent to the same quadrant as the initial cancer, implying that tumor recurrence may be caused by residual cancer cells and/or quiescent cancer stem cells (CSCs) in the tumor. We hypothesized that wound fluid (WF) collected after modified radical mastectomy (MRM) may activate cancer cells and CSCs, promoting epithelial mesenchymal transition (EMT) and invasion. Therefore, we characterized the cytokinome of WF drained from post-MRM cavities of non-IBC and IBC patients. The WF of IBC patients showed a significantly higher expression of various cytokines than in non-IBC patients. In vitro cell culture models of non-IBC and IBC cell lines were grown in media conditioned with and/without WF for 48 h. Afterwards, we assessed cell viability, the expression of CSCs and EMT-specific genes, and tumor invasion. Genes associated with CSCs properties and EMT markers were regulated in cells seeded in media conditioned by WF. IBC-WF exhibited a greater potential for inducing IBC cell invasion than non-IBC cells. The present study demonstrates the role of the post-surgical tumor cavity in IBC recurrence and metastasis.
炎性乳腺癌（IBC）是一种侵袭性表型，复发率高且生存率低。约90%的局部乳腺癌复发发生在与原发癌相同象限的附近，这意味着肿瘤复发可能是由肿瘤中残留的癌细胞和/或静止的癌症干细胞（CSCs）引起的。我们推测，改良根治性乳房切除术（MRM）后收集的伤口渗出液（WF）可能激活癌细胞和CSCs，促进上皮-间质转化（EMT）和侵袭。因此，我们对非IBC和IBC患者MRM术后腔隙引流的WF的细胞因子组进行了表征。IBC患者的WF显示出比非IBC患者更高的各种细胞因子表达。非IBC和IBC细胞系的体外细胞培养模型在含有和不含有WF的条件培养基中培养48小时。之后，我们评估了细胞活力、CSCs和EMT特异性基因的表达以及肿瘤侵袭。与CSCs特性和EMT标志物相关的基因在接种于WF条件培养基中的细胞中受到调控。与非IBC细胞相比，IBC-WF诱导IBC细胞侵袭的潜力更大。本研究证明了术后肿瘤腔隙在IBC复发和转移中的作用。
