Collagen-rich stroma in aggressive colon tumors induces mesenchymal gene expression and tumor cell invasion.

Gene expression-based classification systems have identified an aggressive colon cancer subtype with mesenchymal features, possibly reflecting epithelial-to-mesenchymal transition (EMT) of tumor cells. However, stromal fibroblasts contribute extensively to the mesenchymal phenotype of aggressive colon tumors, challenging the notion of tumor EMT. To separately study the neoplastic and stromal compartments of colon tumors, we have generated a stroma gene filter (SGF). Comparative analysis of stromahigh and stromalow tumors shows that the neoplastic cells in stromahigh tumors express specific EMT drivers (ZEB2, TWIST1, TWIST2) and that 98% of differentially expressed genes are strongly correlated with them. Analysis of differential gene expression between mesenchymal and epithelial cancer cell lines revealed that hepatocyte nuclear factor 4α (HNF4α), a transcriptional activator of intestinal (epithelial) differentiation, and its target genes are highly expressed in epithelial cancer cell lines. However, mesenchymal-type cancer cell lines expressed only part of the mesenchymal genes expressed by tumor-derived neoplastic cells, suggesting that external cues were lacking. We found that collagen-I dominates the extracellular matrix in aggressive colon cancer. Mimicking the tumor microenvironment by replacing laminin-rich Matrigel with collagen-I was sufficient to induce tumor-specific mesenchymal gene expression, suppression of HNF4α and its target genes, and collective tumor cell invasion of patient-derived colon tumor organoids. The data connect collagen-rich stroma to mesenchymal gene expression in neoplastic cells and to collective tumor cell invasion. Targeting the tumor-collagen interface may therefore be explored as a novel strategy in the treatment of aggressive colon cancer.

Use of bidirectional barbed suture in laparoscopic myomectomy: evaluation of perioperative outcomes, safety, and efficacy.

STUDY OBJECTIVE: To compare perioperative outcomes during laparoscopic myomectomy using a bidirectional barbed suture vs conventional smooth suture. DESIGN: Retrospective analysis of 138 consecutive laparoscopic myomectomies performed by a single surgeon over 3 years (Canadian Task Force classification II-2). SETTING: Major university teaching hospital. PATIENTS: One hundred thirty-eight women with symptomatic uterine myomas. INTERVENTIONS: In women undergoing laparoscopic myomectomy from February 2007 through April 2010, conventional smooth sutures were used in 31 patients, and bidirectional barbed suture in 107 patients. MEASUREMENTS AND MAIN RESULTS: The primary indications for laparoscopic myomectomy in either group were pelvic pain or pressure and abnormal uterine bleeding. Use of bidirectional barbed suture was found to significantly shorten the mean (SD) duration of surgery (118 [53] minutes vs 162 [69] minutes; p <.05) and reduce the duration of hospital stay (0.58 [0.46] days vs 0.97 [0.45] days; p <.05). No significant differences were observed between the 2 groups insofar as incidence of perioperative complications, estimated blood loss, and number or weight of myomas removed during surgery. CONCLUSION: Use of bidirectional barbed suture seems to facilitate closure of the hysterotomy site in laparoscopic myomectomy.