The Role of Myofibroblasts at the Tumor Border of Invasive Colorectal Adenocarcinomas

Abstract

Background:In order to elucidate the significance of myofibroblasts in invasive growth of colorectal adenocarcinomas, we examined the number of myofibroblasts at the tumor border of colorectal adenocarcinomas.Method: A total of 91 invasive colorectal adenocarcinomas were examined immunohistochemically using anti-alpha-smooth muscle actin (ASMA) and high-molecular-weight caldesmon (h-CD) antibodies; 25 carcinomas confined to the submucosa (sm carcinomas), 40 carcinomas confined to the muscularis propria (mp carcinomas) and 26 carcinomas invading the subserosa or adventitia (ss carcinomas). We considered ASMA-positive and h-CD-negative stromal cells as myofibroblasts.Results: Twenty-seven (67%) of the 40 mp carcinomas and 25 (96%) of the 26 ss carcinomas had a small number of myofibroblasts at the tumor border facing the muscularis propria. Conclusions:Although direct evidence is lacking, there is a possibility that the further immediately vertical and radial invasion of carcinoma cells into the subserosa or adventitia is associated with a smaller number of myofibroblasts at the tumor border facing the muscularis propria in mp carcinomas, resulting in a low incidence of mp and a high incidence of ss carcinomas in the colorectum.

Invasion and MMP expression profile in desmoid tumours

“…Besides the vascular, immune and inflammatory cells, the microenvironment of a tumour consists mainly of myofibroblasts. An important role for myofibroblasts was suggested by the fact that large numbers of myofibroblasts were found near the invasive front of colon cancer or other invasive carcinomas (Nakayama et al, 1998). Recently, it became evident that MMPs are mostly produced by stromal cells and not by the cancer cells (Noël et al, 2001).…”

Role of tissue stroma in cancer cell invasion

“…Immunocytochemical characterization of myofibroblasts is based on a combination of different markers, such as positivity for α-smooth muscle actin (SMA), vimentin, prolyl 4-hydroxylase ( Figure 3) and absence of cytokeratin. Smoothelin and high-molecular-weight caldesmon are expressed in smooth muscle cells but not in myofibroblasts [88][89][90]. CLIC4, a transport protein belonging to the chloride intracellular channel family, is expressed in TGF-β-treated primary breast fibroblasts but not in untreated primary breast fibroblasts [91].…”

Comparison of Myofibroblasts Expression in Oral Squamous Cell Carcinoma, Verrucous Carcinoma, High Risk Epithelial Dysplasia, Low Risk Epithelial Dysplasia and Normal Oral Mucosa

“…The stromal myofibroblast reaction to many invasive and metastatic carcinomas may constitute a third, albeit more primitive, response [4]. The collagen produced by the myofibroblasts was initially thought to signify an attempt to entrap the neoplasm and impede vascular invasion [5]. A more recently held view is that tumor progression results from an aberrant communication between cancer cells and their microenvironment.…”

“…These cells are believed to be derived from normal fibroblasts during times of tissue stress or altered homeostasis and are defined immunohistochemically by the presence of a-smooth muscle actin (a-SMA), vimentin, smooth muscle myosin heavy chain, desmin, calponin, and a1-integrin. Host cells and the ECM in the tumor may positively or negatively influence tumor progression [5].…”