Abstract
Although CD133 has been reported to be a promising colon cancer stem cell marker, the biological functions of CD133+ colon cancer cells remain controversial. In the present study, we investigated the biological differences between CD133+ and CD133− colon cancer cells, with a particular focus on their interactions with cancer-associated fibroblasts, especially CD10+ fibroblasts. We used 19 primary colon cancer tissues, 30 primary cultures of fibroblasts derived from colon cancer tissues and 6 colon cancer cell lines. We isolated CD133+ and CD133− subpopulations from the colon cancer tissues and cultured cells. In vitro analyses revealed that the two populations showed similar biological behaviors in their proliferation and chemosensitivity. In vivo analyses revealed that CD133+ cells showed significantly greater tumor growth than CD133− cells (P = 0.007). Moreover, in cocultures with primary fibroblasts derived from colon cancer tissues, CD133+ cells exhibited significantly more invasive behaviors than CD133− cells (P<0.001), especially in cocultures with CD10+ fibroblasts (P<0.0001). Further in vivo analyses revealed that CD10+ fibroblasts enhanced the tumor growth of CD133+ cells significantly more than CD10− fibroblasts (P<0.05). These data demonstrate that the in vitro invasive properties and in vivo tumor growth of CD133+ colon cancer cells are enhanced in the presence of specific cancer-associated fibroblasts, CD10+ fibroblasts, suggesting that the interactions between these specific cell populations have important roles in cancer progression. Therefore, these specific interactions may be promising targets for new colon cancer therapies.
Highlights
Colorectal cancer is the second leading cause of cancer-related death in the Western world and its incidence is increasing in Asian countries as a result of changes toward a westernized diet [1]
We investigated the biological implications of CD133+ colon cancer cells by analyzing CD133 expression in human primary colon cancer tissues and evaluating the biological behaviors of CD133+ and CD1332 cells derived from colon cancer cell lines in vitro and in vivo
We investigated the percentages of the CD133+ and CD1332 cell populations in primary colon cancer tissues by flow cytometry
Summary
Colorectal cancer is the second leading cause of cancer-related death in the Western world and its incidence is increasing in Asian countries as a result of changes toward a westernized diet [1]. The concept of cancer stem cells (CSCs) has been focused upon in the biology of colorectal cancer. Colon cancer shows a marked degree of morphological and functional heterogeneity in its cells. Among these cell populations, CSCs in particular have been reported to possess tumorigenic and treatment-resistant activities [2]. The biological functions of CD133 remain unknown [7], CD133 alone or in combination with other markers is currently used to isolate stem cells from numerous tissues [4,5], as well as the prostate [8], liver [9] and pancreas [10,11]. The implications of CD133 as a CSC marker remain controversial
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