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Cancer‐associated fibroblasts (CAFs) in the tumor microenvironment play major roles in supporting cancer progression. A previous report showed that SPIN90 downregulation is correlated with CAF activation and that SPIN90‐deficient CAFs promote breast cancer progression. However, the mechanisms that mediate cancer‐stroma interaction and how such interactions regulate cancer progression are not well understood. Here, we show that extra domain A (EDA)‐containing fibronectin (FN), FN(+)EDA, produced by mouse embryonic fibroblasts (MEFs) derived from Spin90‐knockout (KO) mice increases their own myofibroblast differentiation, which facilitates breast cancer progression. Increased FN(+)EDA in Spin90‐KO MEFs promoted fibril formation in the extracellular matrix (ECM) and specifically interacted with integrin α4β1 as the mediating receptor. Moreover, FN(+)EDA expression by Spin90‐KO MEFs increased proliferation, migration, and invasion of breast cancer cells. Irigenin, a specific inhibitor of the interaction between integrin α4β1 and FN(+)EDA, significantly blocked the effects of FN(+)EDA, such as fibril formation by Spin90‐KO MEFs and proliferation, migration, and invasion of breast cancer cells. In orthotopic breast cancer mouse models, irigenin injection remarkably reduced tumor growth and lung metastases. It was supported by that FN(+)EDA in assembled fibrils was accumulated in cancer stroma of human breast cancer patients in which SPIN90 expression was downregulated. Our data suggest that SPIN90 downregulation increases FN(+)EDA and promotes ECM stiffening in breast cancer stroma through an assembly of long FN(+)EDA‐rich fibrils; moreover, engagement of the Integrin α4β1 receptor facilitates breast cancer progression. Inhibitory effects of irigenin on tumor growth and metastasis suggest the potential of this agent as an anticancer therapeutic. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether percutaneous transthoracic needle biopsy (PTNB) increased the risk of pleural recurrence in stage I non-small-cell lung cancer (NSCLC).Methods: In this retrospective study, we reviewed 830 consecutive patients with stage I NSCLC who underwent curative resection between 2004 and 2010. Cox regression analyses with propensity score matching were performed to identify risk factors for pleural recurrence.Results: Of 830 patients, 540 (65.1%) underwent PTNB before surgery, while 290 (34.9%) underwent preoperative bronchoscopic biopsy or intraoperative wedge resection for a pathological diagnosis. Concomitant pleural recurrence occurred in 42 patients (5.1% [95% CI, 3.8-6.8]; 34 [6.3%] PTNB patients and eight [2.8%] non-PTNB patients) and isolated pleural recurrence took place in 26 patients (3.1% [95% CI, 2.1-4.6]; 20 [3.7%] PTNB patients and 6 [2.1%] non-PTNB patients). On multivariate analysis after matching, only visceral pleural invasion was associated with concomitant pleural recurrence (hazard ratio [HR]=3.367; 95% CI, 1.262-8.986; p=0.015) and isolated pleural recurrence (HR=3.216; 95% CI, 1.037-9.978; p=0.043), while PTNB was associated with neither concomitant nor isolated pleural recurrence (p=0.605 and p=0.963, respectively). Among 540 patients undergoing PTNB, the transfissural approach did not have a significant association with pleural recurrence (p=0.539 and p=0.313, respectively); instead, visceral pleural invasion and microscopic lymphatic invasion were significantly associated with concomitant pleural recurrence, and microscopic lymphatic invasion was associated with isolated pleural recurrence (p<0.05).Conclusion: PTNB did not significantly increase the risk of pleural recurrence in stage I NSCLC, whereas visceral pleural invasion was responsible for pleural recurrence.Key Points: • PTNB did not significantly increase the risk of pleural recurrence in stage I NSCLC, whereas visceral pleural invasion was responsible for pleural recurrence. • The transfissural approach in PTNB did not increase the risk of pleural recurrence. • PTNB can be performed for the confirmatory diagnosis of peripheral stage I lung cancer without concern for the risk of pleural recurrence. [ABSTRACT FROM AUTHOR]

Objective: The objective of our study was to determine whether visceral pleural invasion (VPI) of T1-sized peripheral pulmonary adenocarcinomas manifesting as subsolid nodules (SSNs) abutting the pleural surface or associated with pleural tags can be predicted., Materials and Methods: Our study population consisted of 188 T1-sized peripheral pulmonary adenocarcinomas that appeared as SSNs (24 pure ground-glass nodules [GGNs] and 164 part-solid nodules) and underwent surgical resection between January 2007 and December 2013. Logistic regression analysis was performed to identify significant factors in predicting VPI., Results: VPI occurred in 36 of 188 adenocarcinomas (19.1%). There were no cases of VPI in patients with pure GGNs. In part-solid nodules, there were significant differences regarding the presence of pleural contact, presence of pleural thickening, presence of solid portion abutting the pleura, nodule size, solid portion size, solid proportion, interface length, and length of the solid portion contacting the pleura (p < 0.05). Multivariate analysis revealed pleural contact (p < 0.001), pleural thickening (p = 0.003), solid proportion greater than 50% (p = 0.002), and nodule size greater than 20 mm (p = 0.015) as significant independent predictive features for VPI with adjusted odds ratios of 8.300, 3.966, 4.636, and 2.993, respectively., Conclusion: In part-solid nodules, the CT features of pleural contact, pleural thickening, solid proportion greater than 50%, and nodule size greater than 20 mm were shown to be significant indicators of VPI by T1-sized peripheral adenocarcinomas.