Milky spots in the greater omentum are predominant sites of local tumour cell proliferation and accumulation in the peritoneal cavity

Krist, Lambert F. G.; Kerremans, Miranda; Broekhuis-Fluitsma, Donna M.; Eestermans, I.L.; Meyer, S.; Beelen, Robert H.J.

doi:10.1007/s002620050522

Cited by 55 publications

(53 citation statements)

References 12 publications

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“…Histologically, macrophages that accumulate around tumors are believed to be TAMs. Results from studies using mouse models have shown that secondary metastases are derived from newly generated milky spots that appear around the first metastatic spots (14). Therefore, the accumulation of foci of inflammatory cells would act as ''soil'' for the growth of cancer cells as ''seed'' (45).…”

Section: Discussionmentioning

confidence: 99%

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A Carbohydrate Recognition–Based Drug Delivery and Controlled Release System using Intraperitoneal Macrophages as a Cellular Vehicle

et al. 2006

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The lymphoid tissue in the omentum, at the so-called milky spots, is known as an initial place for disseminated cancer cells to develop into solid tumors. In the present study, i.p. macrophages significantly took up oligomannose-coated liposomes (OMLs) that were injected into the peritoneal cavity, and then gradually accumulated in the omentum and the other lymphoid tissues within 24 hours of i.p. injection of OMLs. When 5-fluorouracil (5-FU) was encapsulated in the OMLs, >60% of administered 5-FU accumulated in the omentum. Treatment of macrophages at 39°C for 30 minutes led to the release of 5-FU from the macrophages, suggesting that controlled release from macrophages could be achieved by mild hyperthermia. We encased magnetic nanoparticles, which are known to convert electromagnetic energy to heat in the OMLs to achieve in vivo hyperthermia at the site. Using this system in a mouse i.p. metastasis model, we successfully controlled tumor development by coadministration of OML-encased 5-FU and OML-encased magnetic nanoparticles, followed by treatment with an alternating magnetic field. No apparent reduction was seen in tumor growth with the administration of OML-encased magnetic nanoparticles or OML-encased 5-FU alone. Thus, we have established the use of i.p. macrophages as a novel drug delivery system for the control of cancer metastatic to milky spots. (Cancer Res 2006; 66(17): 8740-8)

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Section: Discussionmentioning

confidence: 99%

“…Omentectomy is widely done to reduce the risk of recurrence and to improve survival (9,10). In addition, in a series of experimental studies, the omentum seemed to act as an initial implantation site for malignant cells (8,(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

A Carbohydrate Recognition–Based Drug Delivery and Controlled Release System using Intraperitoneal Macrophages as a Cellular Vehicle

et al. 2006

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“…This attachment has been observed for numerous cell lines in our study and is consistent with other investigations indicating that it occurs in diverse species including mice, rats, and humans. 6,7 The mechanisms responsible for the specific attachment remain to be determined. It is not clear whether the known filtering capacity of the immune aggregates 49 is involved in the attachment process or whether specific receptor/ligand pairs are required.…”

Section: Discussionmentioning

confidence: 99%

“…Despite this apparent immune function, tumor cells can bind to the aggregates, suggesting that these sites may play an important role in peritoneal metastatic disease. 5,6,19,20 A primary tumor may shed a large number of metastatic tumor cells each day, yet only a few of these cells will actually develop into metastases. 21 Metastatic development is dependent on the acquisition of traits that promote survival by the tumor cells themselves as well as properties of the target tissue.…”

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confidence: 99%

Preferential Attachment of Peritoneal Tumor Metastases to Omental Immune Aggregates and Possible Role of a Unique Vascular Microenvironment in Metastatic Survival and Growth

Gerber

Rybalko

Bigelow

et al. 2006

The American Journal of Pathology

169

157

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Controlling metastases remains a critical problem in cancer biology. Within the peritoneal cavity, omental tissue is a common site for metastatic disease arising from intraperitoneal tumors; however, it is unknown why this tissue is so favorable for metastatic tumor growth. Using five different tumor cell lines in three different strains of mice, we found that the omentum was a major site of metastases growth for intraperitoneal tumors. Furthermore, initial attachment and subsequent growth were limited to specific sites within the omentum, consisting of organized aggregates of immune cells. These immune aggregates contained a complex network of capillaries exhibiting a high vascular density, which appear to contribute to the survival of metastatic cells. We found that the vasculature within these aggregates contained CD105؉ vessels and vascular sprouts, both indicators of active angiogenesis. A subset of mesothelial cells situated atop the immune aggregates was found to be hypoxic, and a similar proportion was observed to secrete vascular endothelial growth factor-A. These data provide a physiological mechanism by which metastatic tumor cells preferentially grow at sites rich in proangiogenic vessels, apparently stimulated by angiogenic factors produced by mesothelial cells. These sites provide metastatic cells with a microenvironment highly conducive to survival and subsequent growth.

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“…Although myofibroblasts have been reported to derive from resident peritoneal fibroblasts, human peritoneal mesothelial cells (hPMCs) (16,17), bone marrow progenitor cells or the primary tumor itself (18,19), the origin of these myofibroblasts has not been clearly established. Also, during the initial stages of peritoneal (20)(21)(22)(23). Thus, the interactions between cancer cells derived from the primary tumor and submesothelium layer components such as myofibroblasts may be a key to peritoneal dissemination (24).…”

Section: Introductionmentioning

confidence: 99%

Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer

Akagawa

Ohuchida

Torata

et al. 2014

International Journal of Oncology

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Abstract. Myofibroblasts in the stroma of pancreatic cancers promote tumor proliferation, invasion and metastasis by increasing extracellular matrix and secretion of several growth factors. In contrast, the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer has not yet been determined. This study was designed to assess the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer. Three primary cultures of human peritoneal myofibroblasts (hPMFs) were established from disseminated sites of pancreatic cancer and their interactions with the SUIT-2 and CAPAN-1 human pancreatic cancer cell lines were analyzed in vitro. Using a model in BALB/c nu/nu mice, we compared the dissemination ability of intraperitoneally implanted pancreatic cancer cells, with and without hPMFs, and examined the presence of green fluorescent protein (GFP)-labeled hPMFs at peritoneally disseminated sites in mice. hPMFs significantly promoted the migration and invasion of pancreatic cancer cells (P<0.05), while the cancer cells significantly promoted the migration and invasion of hPMFs (P<0.05). In vivo, the number of peritoneally disseminated nodules, more than 3 mm in size, was significantly greater in mice implanted with cancer cells plus hPMFs compared to mice implanted with cancer cells alone, with GFP-labeled hPMFs surviving in the peritoneal cavity of the former. hPMFs promote the peritoneal dissemination of pancreatic cancer. The cancer-stromal cell interaction in the peritoneal cavity may be a new therapeutic target to prevent the dissemination of pancreatic cancer.

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Milky spots in the greater omentum are predominant sites of local tumour cell proliferation and accumulation in the peritoneal cavity

Cited by 55 publications

References 12 publications

A Carbohydrate Recognition–Based Drug Delivery and Controlled Release System using Intraperitoneal Macrophages as a Cellular Vehicle

A Carbohydrate Recognition–Based Drug Delivery and Controlled Release System using Intraperitoneal Macrophages as a Cellular Vehicle

Preferential Attachment of Peritoneal Tumor Metastases to Omental Immune Aggregates and Possible Role of a Unique Vascular Microenvironment in Metastatic Survival and Growth

Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer

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