Background:Colorectal cancer (CRC) is a leading cause of death in the United States. Increased level of interleukin-8 (IL-8) and CXCR2 on tumours and in the tumour microenvironment has been associated with CRC growth, progression and recurrence in patients. Here, we aimed to evaluate the effects of tissue microenvironment-encoded IL-8 and CXCR2 on colon cancer progression and metastasis.Methods:A novel immunodeficient, skin-specific IL-8-expressing transgenic model was generated to evaluate colon cancer growth and metastasis. Syngeneic mouse colon cancer cells were grafted in CXCR2 knockout (KO) mice to study the contribution of CXCR2 in the microenvironment to cancer growth.Results:Elevated levels of IL-8 in the serum and tumour microenvironment profoundly enhanced the growth of human and mouse colon cancer cells with increased peri-tumoural angiogenesis, and also promoted the extravasation of the cancer cells into the lung and liver. The tumour growth was inhibited in CXCR2 KO mice with significantly reduced tumour angiogenesis and increased tumour necrosis.Conclusion:Increased expression of IL-8 in the tumour microenvironment enhanced colon cancer growth and metastasis. Moreover, the absence of its receptor CXCR2 in the tumour microenvironment prevented colon cancer cell growth. Together, our study demonstrates the critical roles of the tumour microenvironment-encoded IL-8/CXCR2 in colon cancer pathogenesis, validating the pathway as an important therapeutic target.

Background Ulcerative colitis (UC) is characterized by continuous mucosal inflammation extending from rectum to the proximal lesion. However, there are cases of atypical distribution of inflammation, such as appendiceal orifice inflammation (AOI), skipped lesion, and rectal sparing. This study aimed to evaluate the prevalence and clinical course of atypical distribution of inflammation in newly diagnosed UC. Methods Between 2013 and 2021, 374 patients who underwent a colonoscopy at the time of diagnosis of UC were retrospectively reviewed. Clinical courses including relapse rate within 1-year, 2-year of diagnosis and exposure to immunomodulator or biologics during follow-up were retracted from the prospective IBD registry (ClinicalTrial.gov, NCT02193464). Atypical UC was defined as patients with AOI, skipped lesion or rectal sparing at initial colonoscopy. The clinical courses and changes of endoscopic findings were compared between typical UC group and atypical UC group. Results Of 374 patients, 116 (31.0%) categorized as atypical UC; specifically, 90 (24.1%) showed AOI, 17 (4.5%) showed rectal sparing and 49 (13.1%) showed skipped lesion. When 90 patients with AOI were reclassified according to the extent of inflammation, 62(16.6%) had a localized inflammation at peri-appendiceal area, 13(3.5%) had an inflammation of the entire cecum, 15(4.0%) had an inflammation extends to the proximal A-colon. The clinical courses of atypical UC were not different from typical UC group, however, patients with skipped lesion showed a lower 1-year relapse rate compared to those without skipped lesion (P=0.042). Of 96 patients with atypical UC who underwent follow-up endoscopy, 73 (75.8%) demonstrated a typical distribution of UC at their follow-up colonoscopy. Conclusion Atypical distribution of UC including AOI, skipped lesion, and rectal sparing are not uncommon in patient with newly diagnosed UC. However, most of these features do not appear to correlate significantly with prognosis in the clinical course of UC. In majority of patients with atypical UC, the lesion turned into typical UC on follow-up colonoscopy.