Tumor cell can be significantly influenced by various chemical groups of the extracellular matrix proteins. However, the underlying molecular mechanisms involved in the interaction between cancer cells and functional groups in the extracellular matrix remain unknown. Using chemically modified surfaces with biological functional groups (CH 3 , NH 2 , OH), it was found that hydrophobic surfaces modified with CH 3 and NH 2 suppressed cell proliferation and induced the number of apoptotic cells. Mitochondrial dysfunction, cytochrome c release, Bax upregulation, cleaved caspase-3 and PARP, and Bcl-2 downregulation indicated that hydrophobic surfaces with CH 3 and NH 2 triggered the activation of intrinsic apoptotic signaling pathway. Cells on the CH 3 - and NH 2 -modified hydrophobic surfaces showed downregulated expression and activation of integrin β1, with a subsequent decrease of focal adhesion kinase (FAK) activity. The RhoA/ROCK/PTEN signaling was then activated to inhibit the phosphorylation of PI3K and AKT, which are essential for cell proliferation. However, pretreatment of MDA-MB-231 cells with SF1670, a PTEN inhibitor, abolished the hydrophobic surface-induced activation of the intrinsic pathway. Taken together, the present results indicate that CH 3 - and NH 2 -modified hydrophobic surfaces induce mitochondria-mediated apoptosis by suppressing the PTEN/PI3K/AKT pathway, but not OH surfaces. These findings are helpful to understand the interaction between extracellular matrix and cancer cells, which might provide new insights into the mechanism potential intervention strategies for tumor prognosis.
Osseointegration of implants is a complex physiological process that requires temporal and spatial regulation of immune responses, angiogenesis , and osteogenesis. To achieve efficient and long-term osseointegration, type I collagen (COL1) decorated nanoporous network was developed on titanium substrates via alkali treatment , polydopamine coating, and layer-by-layer (LBL) self-assembly. It was noted that the simple physisorbed COL1 could be easily desorbed from the nanostructured surface , however, multilayer COL1 constructed by polydopamine and LBL self-assembly obscured the nanoporous network of the alkali-treated titanium surfaces. Interestingly, the nanostructured surface covalently immobilized with COL1 (T-ADC) could timely convert macrophages (MΦs) from pro-inflammatory M1 to pro-healing M2 phenotype, generating a beneficial osteoimmune microenvironment and promoting angio/osteo-genesis. RNA sequencing revealed that the nanostructure and COL1 could synergistically activate RhoA/ROCK, PI3K-AKT, and classical MAPK signaling pathways in MΦs to sustain the cell cycle, and trigger autocrine feedback-mediated JAK-STAT and FoxO signaling pathways, which in turn motivated autophagy and oxidative stress resistance and attenuated lipopolysaccharide-induced Toll-like receptor signaling pathway and its downstream NF-κB and JNK/p38 MAPK signaling cascades, leading to the inhibition of inflammation and osteoclastic-related gene expression of MΦs. Simultaneously, T-ADC prominently facilitated angiogenesis of endothelial cells and osteogenesis of osteoblasts as well as their cross-talks, further highlighting synergistically positive effects of the nanostructure and COL1 on osseointegration. In vivo experiments revealed that T-ADC could induce abundant new bone mass and ameliorative osseointegration, corroborating the in vitro results. The study elucidated that the COL1 decorated nanoporous network on titanium surfaces could significantly regulate early inflammatory reaction and subsequent angio/osteo-genesis processes, resulting in favorable osseointegration.
危险品化学品经营许可证（带存储）