Contribution of Interstitial Cells of Cajal to Gastrointestinal Stromal Tumor Risk

Gastrointestinal stromal tumors originate from interstitial cells of Cajal, the pacemaker cells of the gut. Ca2+ regulates the pacemaker activity of interstitial cells of Cajal. Store-operated Ca2+ entry mediates the majority of Ca2+ entry in most cancer cells and may be a factor in regulating intracellular Ca2+ in interstitial cells of Cajal and gastrointestinal stromal tumors. Therefore, a blockade of this mechanism may affect the progression of gastrointestinal stromal tumors. Orai1 is the pore subunit of store-operated Ca2+ channels. Here, we reported that Orai1 was overexpressed in gastrointestinal stromal tumor tissues and was positively correlated with a high-risk grade in gastrointestinal stromal tumor patients. Furthermore, upon Orai1 silencing, the functional store-operated Ca2+ entry in gastrointestinal stromal tumor cells was decreased, indicating that the function of store-operated Ca2+ entry was mediated by Orai1. Inhibition of Orai1-mediated store-operated Ca2+ entry by Orai1 silencing or store-operated Ca2+ entry blockers (SKF-96365 and 2-aminoethyl diphenylborate) induced obvious cell proliferation suppression, cell-cycle distribution, and apoptosis stimulation in GIST-T1 cells. Conversely, Orai1 overexpression increased store-operated Ca2+ entry and cell proliferation in GIST882 cells. In addition, we found that activation of c-KIT and the extracellular signal–regulated kinase pathway participated in the oncogenic functions of Orai1-mediated store-operated Ca2+ entry in gastrointestinal stromal tumor cells. These results revealed that Orai1-mediated store-operated Ca2+ entry is critical for gastrointestinal stromal tumor cell proliferation via c-KIT and ERK signaling pathway activation. Orai1-mediated store-operated Ca2+ entry plays an oncogenic role and may be a novel prognostic factor and therapeutic target for patients with gastrointestinal stromal tumors.

Download Full-text

Gastroparesis occuring post resection of a gastrointestinal stromal tumor arising from the interstitial cells of cajal (gastric pacemaker cells)

The American Journal of Gastroenterology ◽

10.1016/s0002-9270(01)02933-1 ◽

2001 ◽

Vol 96 (9) ◽

pp. S62

Author(s):

C SALTIN

Keyword(s):

Gastrointestinal Stromal Tumor ◽

Interstitial Cells Of Cajal ◽

Interstitial Cells ◽

Stromal Tumor ◽

Pacemaker Cells ◽

Gastric Pacemaker ◽

Cells Of Cajal

Download Full-text

Congenital Gastrointestinal Pacemaker Cell Tumor

Archives of Pathology & Laboratory Medicine ◽

10.5858/1999-123-0842-cgpct ◽

1999 ◽

Vol 123 (9) ◽

pp. 842-845 ◽

Cited By ~ 3

Author(s):

Sandy S. Wu ◽

Terry L. Buchmiller ◽

Pamelyn Close ◽

George B. Gershman ◽

Shi-Kaung Peng ◽

...

Keyword(s):

Gastrointestinal Stromal Tumor ◽

Interstitial Cells Of Cajal ◽

English Language ◽

Epithelioid Cell ◽

Cell Tumor ◽

Stromal Tumor ◽

Pacemaker Cell ◽

Wall Function ◽

Pediatric Case ◽

Cells Of Cajal

Abstract The interstitial cells of Cajal complex within the gut wall function as a pacemaker to direct peristalsis. Their neoplastic counterpart is the gastrointestinal pacemaker cell tumor, a spindle and/or epithelioid cell mesenchymal tumor previously known as gastrointestinal stromal tumor or incorrectly called leiomyosarcoma in some cases of older reports. Although numerous cases of gastrointestinal leiomyosarcomas have been documented in the English-language literature, no pediatric case of gastrointestinal stromal tumor or gastrointestinal pacemaker cell tumor has, to our knowledge, been recorded. Herein, we report a case of congenital gastrointestinal pacemaker cell tumor confirmed by immunohistochemistry and electron microscopy in a full-term male newborn.

Download Full-text

Successful Perioperative and Surgical Treatment of a Rare Case of Extra-Gastrointestinal Stromal Tumor Arising in the Prostate Gland

Case Reports in Oncology ◽

10.1159/000496686 ◽

2019 ◽

Vol 12 (1) ◽

pp. 183-191 ◽

Cited By ~ 2

Author(s):

Patrick Schöffski ◽

Raf Sciot ◽

Maria Debiec-Rychter ◽

Johan Van Ongeval ◽

André D'Hoore ◽

...

Keyword(s):

Gastrointestinal Stromal Tumor ◽

Prostate Gland ◽

Interstitial Cells ◽

Stromal Tumor ◽

Imatinib Treatment ◽

Smooth Muscle Contractility ◽

Double Mutation ◽

Primary Gist ◽

Common Precursor ◽

Cells Of Cajal

We report a very uncommon case of a primary, non-metastatic gastrointestinal stromal tumor (GIST) arising in the prostate gland in a 60-year-old patient. The morphology and immunohistochemical profile of the disease resembled GIST of gastrointestinal origin, and the molecular driver of this malignancy was a double mutation in exons 11 and 13 of the KIT gene. The tumor was proliferating slowly, did respond to neoadjuvant therapy with the KIT-inhibiting agent imatinib and was cured by radical, retro-pubic prostatectomy followed by adjuvant imatinib treatment. We postulate that primary GIST tumors of the prostate can arise from prostatic interstitial cells, which are the pacemakers of smooth muscle contractility in the gland, and possibly share a common precursor with typical GIST and the interstitial cells of Cajal in the gastrointestinal tract.

Download Full-text

Large Omental Metastases of a Gastrointestinal Stromal Tumor

Medicina ◽

10.3390/medicina47110086 ◽

2011 ◽

Vol 47 (11) ◽

pp. 86

Author(s):

Povilas Ignatavičius ◽

Tomas Petraitis ◽

Žilvinas Saladžinskas ◽

Lilija Butkevičienė ◽

Kristina Žvinienė

Keyword(s):

Case Report ◽

Gastrointestinal Tract ◽

Gastrointestinal Stromal Tumor ◽

Gastrointestinal Stromal Tumors ◽

Interstitial Cells Of Cajal ◽

Metastatic Tumor ◽

Stromal Tumor ◽

Mesenchymal Tumors ◽

Stromal Tumors ◽

Cells Of Cajal

Gastrointestinal stromal tumors are rare tumors, originating from the interstitial cells of Cajal. They are the most common mesenchymal tumors of the gastrointestinal tract. Metastatic tumor is treated with imatinib mesylate. A case of large metastases of a gastrointestinal stromal tumor to the omentum, diagnosis and treatment principles are presented in this case report.

Download Full-text